Antibodies targeted against ILT7 and their uses.

Abstract

Disclosed herein are anti-ILT7 antibodies and antigen-binding fragments, polynucleotides encoding the antibodies and antigen-binding fragments, and pharmaceutical compositions comprising the antibodies and antigen-binding fragments. Uses of the anti-ILT7 antibodies and antigen-binding fragments described herein in treatment of conditions and disorders associated completement activation are also disclosed.

Description

"ANTIBODIES TARGETED AT ILT7 AND THEIR USES" - LINKED TO RELATED APPLICATIONS

[001] This application claims priority over the Application of International Patent No. PCT / CN2023 / 082006, filed on March 16, 2023, the full disclosure of which is incorporated by reference in its entirety for all purposes. REFERENCE TO THE LIST OF SEQUENCES SENT ELECTRONICALLY

[002] This request incorporates by reference a Listing of Sequence as an XML file titled “110961-1435499-018-001-02PCT” created on March 15, 2024, and with a size of 65,204 bytes. FIELD

[003] The present invention relates to molecular biology, cell biology and immunology. Anti-ILT7 antibodies are provided herein and used in the treatment of plasmacytoid dendritic cells (pDCs) or type I interferon-associated immunological disorders (type I IFN). STATE OF THE ART

[004] Plasmacytoid dendritic cells (pDCs), responsible for the production of type I interferons (IFNs) and pro-inflammatory cytokines, are responsible for innate and adaptive immune responses. Both pDCs and type I IFNs are involved in various immunological disorders. ILT7, a member of the immunoglobulin-like (ILT) family of transcribed genes or leukocyte immunoglobulin-like receptors (LIRs), is selectively expressed on pDCs. Thus, ILT7-targeted agents that can suppress the release of type I IFN associated with pDCs are needed, for example, to treat and prevent autoimmune diseases. However, there has been limited success in developing such ILT7-targeted agents. The compositions and methods provided in this document meet these needs and offer relative advantages. Petition 870250083106, dated 09 / 15 / 2025, pp. 152 / 354 2 / 171 SUMMARY

[005] The terms “invention,” “the invention,” “this invention,” and “the present invention,” as used in this document, are intended to refer broadly to the entire subject matter of this patent application and the claims below. Statements containing these terms should be understood as not limiting the subject matter described in this document or limiting the meaning or scope of the patent claims below. The encompassed embodiments of the invention are defined by the claims, not by this summary. This summary is a high-level overview of various aspects of the invention and introduces some of the concepts described and illustrated in this document and the accompanying figures. This summary is not intended to identify essential or key features of the claimed subject matter, nor should it be used in isolation to determine the scope of the claimed subject matter.The subject matter should be understood by reference to appropriate parts of the entire specification, any or all of the figures, and according to the claim. Some exemplary embodiments of the present invention are discussed below.

[006] Antibodies or antigen-binding fragments specifically binding to human ILT7 are provided in this document, the antibodies or antigen-binding fragments comprising: (1) as defined by Kabat, (a) a variable light chain (VL) region comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in the VL CDRs; and / or (b) a variable heavy chain (VH) region comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in the VH CDRs; or (2) as defined by Chothia, (a) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12, and 13, respectively;or a variant thereof having up to about 5 substitutions; Petition 870250083106, dated 09 / 15 / 2025, pp. 153 / 354 3 / 171 amino acid additions and / or deletions in VL CDRs; and / or (b) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 17, 18, and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions, and / or deletions in VH CDRs.

[007] In some embodiments, the antibodies or antigen-binding fragments provided in this document comprise VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2, and VH CDR3 with the amino acid sequences of SEQ ID NOs: 11, 12, 13, 14, 15, and 16, respectively, as defined by Kabat. In some embodiments, the antibodies or antigen-binding fragments provided in this document comprise VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2, and VH CDR3 with the amino acid sequences of SEQ ID NOs: 11, 12, 13, 17, 18, and 16, respectively, as defined by Chothia.

[008] Also provided in this document are antibodies or antigen-binding fragments that bind specifically to human ILT7, the antibodies or antigen-binding fragments comprising: (a) a VL with at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH with at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 10. In some embodiments, the antibodies or antigen-binding fragments provided in this document comprise a VL and a VH with the amino acid sequences of SEQ ID NOs: 9 and 10, respectively.

[009] Also provided in this document are antibodies or antigen-binding fragments that bind specifically to human ILT7, the antibodies or antigen-binding fragments comprising (a) a VL comprising CDR1, VL CDR2, and VL CDR3 of a VL having the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH comprising Petition 870250083106, dated 09 / 15 / 2025, pp. 154 / 354 4 / 171 VH CDR1, VH CDR2 and VH CDR3 of a VH having the amino acid sequence SEQ ID NO: 10.

[0010] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are chimeric antibodies or antigen-binding fragments, humanized antibodies or antigen-binding fragments, or human antibodies or antigen-binding fragments.

[0011] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are humanized antibodies or antigen-binding fragments. In some embodiments, the humanized anti-ILT7 antibodies or antigen-binding fragments comprise: (a) a VL having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22; and / or (b) a VH having at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 23-28.

[0012] In some embodiments, the humanized anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise a VL and a VH with the amino acid sequences of (1) SEQ ID NOs: 19 and 23, respectively; (2) SEQ ID NOs: 19 and 24, respectively; (3) SEQ ID NOs: 19 and 25, respectively; (4) SEQ ID NOs: 19 and 26, respectively; (5) SEQ ID NOs: 19 and 27, respectively; (6) SEQ ID NOs: 19 and 28, respectively; (7) SEQ ID NOs: 20 and 23, respectively; (8) SEQ ID NOs: 20 and 24, respectively; (9) SEQ ID NOs: 20 and 25, respectively; (10) SEQ ID NOs: 20 and 26, respectively; (11) SEQ ID NOs: 20 and 27, respectively; (12) SEQ ID NOs: 20 and 28, respectively; (13) SEQ ID NOs: 21 and 23, respectively; (14) SEQ ID NOs: 21 and 24, respectively; (15) SEQ ID NOs: 21 and 25, respectively; (16) SEQ ID NOs: 21 and 26, respectively; (17) SEQ ID NOs: 21 and 27, respectively; (18) SEQ ID NOs: Petition 870250083106, dated 09 / 15 / 2025, pp. 155 / 354 5 / 171 and 28, respectively; (19) SEQ ID NOs: 22 and 23, respectively; (20) SEQ ID NOs: 22 and 24, respectively; (21) SEQ ID NOs: 22 and 25, respectively; (22) SEQ ID NOs: 22 and 26, respectively; (23) SEQ ID NOs: 22 and 27, respectively; or (24) SEQ ID NOs: 22 and 28, respectively.

[0013] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are selected from the group consisting of a Fab, a Fab', an F(ab')2, an Fv, an scFv, a (scFv)2, a single-domain antibody (sdAb), and a heavy-chain antibody (HCAb). In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document may be IgG1 antibodies, IgG2 antibodies, IgG3 antibodies, or IgG4 antibodies.

[0014] In some embodiments, the anti-ILT7 antibodies provided in this document are IgG1 antibodies. In some embodiments, the anti-ILT7 IgG1 antibodies provided in this document comprise a constant region of the light chain (CL) with at least 85% sequence identity to CL kappa (Ck; SEQ ID NO: 29). In some embodiments, the anti-ILT7 IgG1 antibodies provided in this document comprise a constant region of the light chain (CL) with at least 85% sequence identity to CL lambda ^λ; SEQ ID NO: 30).

[0015] In some embodiments, the anti-ILT7 IgG1 antibodies provided in this document comprise a constant heavy chain (HC) region with at least 85% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 31 and 40-44.

[0016] In some embodiments of the anti-ILT7 IgG1 antibodies provided in this document, the constant region of the heavy chain (CH) comprises a wild-type IgG1 CH or comprises at least one amino acid mutation that enhances the ADCC (antibody-dependent cellular cytotoxicity) or ADCP (antibody-dependent cellular phagocytosis) of the antibody. In some embodiments, the CH region of the antibodies Petition 870250083106, dated 09 / 15 / 2025, pp. 156 / 354 6 / 171 The IgG1 molecules provided in this document have an amino acid substitution at L234, L235, G236, S239, F243, H268, D270, R292, S298, Y300, V305, K326, A330, I332, E333, K334, P396, or any combination thereof, numbered according to the EU Index. In some embodiments, the CH region of the IgG1 antibodies provided in this document has an amino acid substitution that is L234Y, L235Q, L235V, G236A, G236W, S239D, S239M, F243L, H268D, D270E, R292P, S298A, Y300L, V305I, K326D, A330M, A330L, I332E, E333A, K334A, K334E or P396L, or any combination thereof, numbered according to the EU Index.In some embodiments of the anti-ILT7 IgG1 antibodies provided in this document, the CH region is modified by amino acid substitutions selected from the group consisting of (i) S298A, E333A and K334A; (ii) S239D and I332E; (iii) S239D, A330L and I332E; (iv) G236A; (v) G236A, S239D and I332E; (vi) G236A, A330L and I332E; (vii) G236A, S239D, A330L and I332E; (viii) F243L, R292P, Y300L, V305I and P396L; (ix) L235V, F243L, R292P, Y300L and P396L; (x) L234Y, L235Q, G236W, S239M, H268D, D270E and S298A; and (xi) D270E, K326D, A330M and K334E, numbered according to the EU Index. In some embodiments, the CH region has an amino acid sequence selected from the group consisting of SEQ ID NOs: 4564.

[0017] In some forms of the anti-ILT7 IgG1 antibodies provided in this document, the Fc group is afucosylated.

[0018] Also provided in this document are antibodies or antigen-binding fragments that compete with an antibody or antigen-binding fragment described in this document for binding to human ILT7.

[0019] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are bispecific antibodies or multispecific antibodies.

[0020] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are monoclonal antibodies or antigen-binding fragments thereof. Petition 870250083106, dated 09 / 15 / 2025, pp. 157 / 354 7 / 171

[0021] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document (1) bind to human ILT7 with a Kd of 500 nM or less, as measured by SPR; (2) do not specifically bind to LILR family members LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3, or LILB5; (3) inhibit the release of interferon alpha (IFNa) by peripheral blood mononuclear cells (PBMCs); (4) selectively bind to plasmacytoid dendritic cells (pDCs) in human PBMCs; (5) exhibit natural killer (NK) cell-dependent ADCC activity against cells expressing ILT7; (6) exhibit neutrophil-dependent ADCC activity against cells expressing ILT7; or (7) exhibit macrophage-dependent ADCP activity against cells expressing ILT7; or any combination of (1)-(7).

[0022] Also provided in this document are anti-ILT7 antibodies or antigen-binding fragments thereof that (1) bind to human ILT7 with a kd of 500 nM or less, as measured by SPR; (2) do not specifically bind to LILR family members LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3 or LILB5; (3) inhibit IFNα release by PBMCs; (4) selectively bind to pDCs on human PBMCs; (5) exhibit NK-dependent ADCC activity against ILT7-expressing cells; (6) exhibit neutrophil-dependent ADCC activity against ILT7-expressing cells; or (7) exhibit macrophage-dependent ADCP activity against cells expressing ILT7; or any combination of (1)-(7).

[0023] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document (1) inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 of 1 nM or less; (2) exhibit NK-dependent ADCC activity against ILT7-expressing cells with an EC50 of 0.01 nM or less; (3) exhibit neutrophil-dependent ADCC activity against ILT7-expressing cells with an Petition 870250083106, dated 09 / 15 / 2025, pp. 158 / 354 8 / 171 EC50 of 100 nM or less; (4) exhibit macrophage-dependent ADCP activity against ILT7-expressing cells with an EC50 of 10 nM or less; or (5) exhibit macrophage-dependent ADCP activity against ILT7-expressing cells with a maximum phagocytic index of 20% or more; or any combination of (1)-(5).

[0024] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document (1) inhibit IFNα release by PBMCs with an EC50 ranging from 0.01 nM to 0.1 nM; (2) exhibit NK-dependent ADCC activity against ILT7-expressing cells with an EC50 ranging from 0.001 nM to 0.01 nM; (3) exhibit neutrophil-dependent ADCC activity against ILT7-expressing cells with an EC50 ranging from 1 nM to 50 nM; (4) exhibit macrophage-dependent ADCP activity against ILT7-expressing cells with an EC50 ranging from 0.5 nM to 5 nM; or (5) exhibit macrophage-dependent ADCP activity against ILT7-expressing cells with a maximum phagocytic index ranging from 20% to 80%; or any combination of (1)-(5).

[0025] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document exhibit neutrophil-dependent ADCC activity.

[0026] Polynucleotides encoding a polypeptide of the anti-ILT7 antibodies or antigen-binding fragments provided in this document are also provided in this document. Vectors comprising the polynucleotide in this document are also provided in this document.

[0027] Host cells comprising the polynucleotide described in this document, or the vector described in this document, are also provided. In some embodiments, the host cells described in this document (1) overexpress N-acetylglucosaminyltransferase III (GnTIII), (2) lack α-1,6-fucosyltransferase (FUT8), or (3) have a low fucose content, or any combination of (1)-(3). Petition 870250083106, dated 09 / 15 / 2025, pp. 159 / 354 9 / 171

[0028] Methods for producing the anti-ILT7 antibodies or antigen-binding fragments described in this document are also provided in this document, the methods comprising culturing the host cell described in this document under conditions that permit expression of the antibody or antibody fragment. In some embodiments, the methods provided in this document comprise isolating the antibody from the culture.

[0029] Pharmaceutical compositions comprising a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments described in this document and a pharmaceutically acceptable carrier are also provided in this document.

[0030] Methods for reducing type I interferon (IFN) in an individual in need of it are also provided in this document; the method comprises administering to the individual a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments described in this document. In some embodiments, type I interferon is IFNa.

[0031] Methods for suppressing or depleting pDCs in an individual who needs them are also provided in this document; the method comprises administering to the individual a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments described in this document.

[0032] Methods for reducing autoimmunity in an individual who needs them are also provided in this document; the method comprises administering to the individual an effective amount of the anti-ILT7 antibodies or antigen-binding fragments described in this document.

[0033] In some modalities of the methods provided in this document, the individual has an autoimmune disease.

[0034] This document also provides treatment methods for an autoimmune disease associated with Type I IFN or pDCs in an individual who requires them; the method comprises administering to Petition 870250083106, dated 09 / 15 / 2025, pp. 160 / 354 10 / 171 individuals receive a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments described in this document.

[0035] In some forms, the autoimmune disease is systemic lupus erythematosus (SLE).

[0036] In some modalities, the methods provided in this document also include the administration of additional therapy to the individual.

[0037] In some modalities of the methods provided in this document, the individual is a human.

[0038] In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments described in this document are provided for the reduction of Type I IFN. Uses of the anti-ILT7 antibodies or antigen-binding fragments described in this document are also provided for the preparation of a medicament to reduce Type I IFN. In some embodiments of the uses provided in this document, Type I IFN is IFNa.

[0039] In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments described herein are provided in this document for the suppression or depletion of pDCs. Uses of the anti-ILT7 antibodies or antigen-binding fragments described herein are also provided in this document for the preparation of a medicament to suppress or deplete pDCs.

[0040] In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments described in this document are provided in this document for reducing autoimmunity. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments described in this document are provided in this document for the preparation of a medicament to reduce autoimmunity.

[0041] In some embodiments, uses of anti-ILT7 antibodies or antigen-binding fragments are provided in this document. Petition 870250083106, dated 09 / 15 / 2025, page 161 / 354 11 / 171 described in this document for the treatment of an autoimmune disease associated with IFN Type I or pDCs. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments described in this document are provided for the preparation of a medicament to treat an autoimmune disease associated with IFN Type I or pDCs. In some embodiments, the autoimmune disease is SLE. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] FIG. 1 provides ELISA results showing the binding of chimeric antibodies ILT7, reference antibody (Tab1) and negative control antibody (hIgG1) to the human ILT7 protein.

[0043] FIGS. 2A-2B provide flow cytometry results showing the binding of chimeric ILT7 antibodies, reference antibody (Tab1) and negative control antibody (hIgG1) to human ILT7 293F cells (FIG. 2A) and CHOK1-cynomolgus ILT7 cells (FIG. 2B).

[0044] FIG. 3 provides representative results of the IFNα release assay in CpG-stimulated PBMCs. The inhibitory activities of the chimeric ILT7 antibodies on IFNα release were measured; the results of the reference antibody (Tab1) and the negative control antibody (hIgG1) are also shown.

[0045] FIGS. 4A-4B provide flow cytometry results showing the binding of chimeric antibodies ILT7cmAb12 (Hu12) and negative control antibody (Tab1) to human ILT7 293F cells (FIG. 4A) and CHOK1-cynomolgus ILT7 cells (FIG. 4B).

[0046] FIGS. 5A-5B provide representative results of the IFN-α release assay in CpG-stimulated PBMCs. The inhibitory activities of four humanized cmAb12 antibodies on IFN-α release were measured, as well as for cmAb12, the reference antibody (Tab1) and the negative control antibody (hIgG1).

[0047] FIG. 6 provides representative results of ELISA measurements of the binding affinities of the hu-cmAb12 antibody, antibody of Petition 870250083106, dated 09 / 15 / 2025, page 162 / 354 12 / 171 reference (Table 1) and negative control antibody (hIgGI) to human ILT7 protein.

[0048] FIGS. 7A-7B provide representative flow cytometry results showing the binding of hu-cmAb12, reference antibody (Tab1) and negative control antibody (isotype) to human ILT7 293F cells (FIG. 7A) and CHOK1-cynomolgus ILT7 cells (FIG. 7B).

[0049] FIG. 8 provides representative flow cytometry results showing the binding of hu-cmAb12, reference antibody (Tab1) and negative control antibody (Isotype) to the ILT7 cell surface in pDCs and other immune cells in human PBMCs.

[0050] FIGS. 9A-9B provide representative results of the IFNα release assay in CpG-stimulated PBMCs (from 4 donors) (graphs and summary table, respectively). The inhibitory activities of hucmAb12 and the reference antibody (Tab1) on IFNα release were measured.

[0051] FIG. 10 provides representative results of the cytotoxic activity assay showing NK cell-dependent ADCC activities of hu-cmAb12, reference antibody (Tab1) and negative control antibody (Isotype).

[0052] FIG. 11 provides representative results of the cytotoxic activity assay showing neutrophil-dependent ADCC activities hucmAb12, reference antibody (Tab1) and negative control antibody (Isotype).

[0053] FIGS. 12A-12B provide representative phagocytosis assay results showing macrophage-dependent ADCP activities of hu-cmAb12, reference antibody (Tab1) and negative control antibody (Isotype) in three donors (graphs and summary table, respectively).

[0054] FIGS. 13A-13B provide representative results of changes in hematological cells after administration of hu-cmAb12, Petition 870250083106, dated 09 / 15 / 2025, page 163 / 354 13 / 171 negative control antibody (Isotype) or PBS infusion into the peripheral blood of humanized mice (FIG. 13A) and cynomolgus monkeys (FIG. 13B). DETAILED DESCRIPTION

[0055] This disclosure provides novel antibodies, including antigen-binding fragments, that bind specifically to ILT7 (e.g., human ILT7). Pharmaceutical compositions comprising a therapeutically effective amount of such antibodies or antigen-binding fragments are also disclosed herein. Also disclosed herein are the uses of such pharmaceutical compositions for the treatment of autoimmune diseases associated with plasmacytoid dendritic cells (pDCs) and / or type I interferon (IFN).

[0056] pDCs are a subpopulation of dendritic cells (DCs) in peripheral blood and secondary lymphoid organs. Although they represent only about 0.1 to 0.8% of peripheral blood mononuclear cells (PBMCs), these cells are drivers of innate and adaptive immune responses. pDCs enhance the innate immune response because they induce chemokines and myeloid cell recruitment, promote monocyte recruitment and differentiation into antigen-presenting cells (APCs), induce dendritic cell maturation and activation, and support natural killer (NK) cell recruitment, activation, and cytotoxicity.pDCs also facilitate adaptive immune responses because they promote antigen presentation, support the activation and expansion of antigen-specific CD4+ Th cells, boost the differentiation of CD4+ T cells into Th2 and Treg cells, promote the survival and activity of CD8+ T cells, and enhance the survival, maturation, differentiation, and autoantibody production of B cells.

[0057] It is important to emphasize that pDCs are the main source of Type I IFNs (α / β), which promote the function of NK cells, B cells, T cells, and myeloid DCs. Both pDCs and Type I IFNs are known to be involved in the development of immunological disorders, such as diseases Petition 870250083106, dated 09 / 15 / 2025, pp. 164 / 354 14 / 171 autoimmune. Eg, Annu. Rev. Pathol. Mech. Dis. 2019, 14:369-93; J Immunol 2020, 205:2941-2950; Clinic Rev Allerg Immunol 59, 248-272 (2020); Front. Immunol. 12:713779; Int. J. Mol. Sci. 2021, 22, 4190; Rheumatology 2017;56:16621675.

[0058] Immunoglobulin-like transcript-7 (ILT7), also known as leukocyte immunoglobulin-like receptor A4 (LIRA4 or LILRA4), or CD85γ, is a member of the immunoglobulin-like transcript (ILT) or leukocyte immunoglobulin-like receptor (LIR) gene family. ILT7 contains four extracellular immunoglobulin-like domains and one transmembrane domain. The extracellular portion is important for interacting with the ILT7 ligand, bone marrow stromal cell antigen 2 (BST2), and the ILT7 transmembrane domain contains a positively charged residue that allows it to bind to FcεRIγ and inhibit pDC function via an ITAM-mediated signaling pathway.

[0059] The complete human ILT7 is a 499-amino acid protein (Uniprot accession number P59901, SEQ ID NO: 1), which contains a signal peptide (amino acids 1-23; removed in the mature protein), an extracellular domain (amino acids 24-446), a transmembrane domain (amino acids 447-467), and a cytoplasmic domain (amino acids 468-499). The extracellular domain includes four immunoglobulin-like C2 domains (amino acids 24-118, 123-213, 224-313, and 324-413). MTLILTSLLFFGLSLGPRTRVQAENLPKPILWAEPGPVITWHNPVTI WCQGTLEAQGYRLDKEGNSMSRHILKTLESENKVKLSIPSMMWEH AGRYHCYYQSPAGWSEPSDPLELVVTAYSRPTLSALPPSPVVTSGV NVTLRCASRLGLGRFTLIEEGDHRLSWTLNSHQHNHGKFQALFPM GPLTFSNRGTFRCYGYENNTPYVWSEPSDPLQLLVSGVSRKPSLL TLQGPVVTPGENLTLQCGSDVGYIRYTLYKEGADGLPQRPGRQPQ AGLSQANFTLSPVSRSYGGQYRCYGAHNVSSEWSAPSDPLDILIA GQISDRPSLSVQPGPTVTSGEKVTLLCQSWDPMFTFLLTKEGAAH Petition 870250083106, dated 09 / 15 / 2025, page 165 / 354 15 / 171 PPLRLRSMYGAHKYQAEFPMSPVTSAHAGTYRCYGSRSSNPYLLS HPSEPLELVVSGATETLNPAQKKSDSKTAPHLQDYTVENLIRMGVA GLVLLFLGILLFEAQHSQRSPPRCSQEANSRKDNAPFRVVEPWEQI (SEQ ID NO: 1)

[0060] More information about human ILT7 can be found in public databases with the following IDs: HGNC: 15503; NCBI Entrez Gene: 23547; Ensembl: ENSG00000239961; OMIM®: 607517; UniProtKB / Swiss-Prot: Q8IZF0. Two transcript variants with alternative splicing encoding different isoforms are described for the human ILT7 gene (Uniprot NOs: P59901-1, P59901-2).

[0061] The ILT7 sequence of cynomolgus is provided below: MTPILTTLLCFGLSLGPRTCLQAENLLKPILWAEPGPVIIWKKPVTIW CQGTLEAQEYRLDKEGNSMLRHMLKTLESENKAKFSIPSMMWEH AGRYHCYYQSPAGWSEPSDPLELVVTAYSRPSLSALPSPVVTSGV NVTLRCASRLGLGRFTLIEEGDHRLSWTLDSHQHNHGKFQALFPV GPLTFSNRGTFRCYGYENNTPYVWSEPSDPLQLLVSGVSRKPSLL TLQGPVVAPGDNLTLQCGSDVGYIRYALYKEGGDGLPQRPGQQS QAGLSQASFTLNPVRGSHGGQYRCYGAHNVSSKWSAPSDPLDILI AGQIPDRPSLSVQLGPTVASGEKVTLLCQSWGPMFTFLLAKEGAA HPPLRLRSTYRAQQYQAEFPMSPVTSAHAGTYRCYGSRSSDPYLL SHSSEPLELVVSEATETLNPAQNKSDSKTAPHLQDYTVENLIRMGI AGLVLVFLGILLFEAQQSQRSPTRCSQEVNSREDNAPFRVVEPWE QI (SEQ ID NO: 2)

[0062] ILT7 is selectively expressed on the surface of human pDCs, and not on myeloid DCs or other peripheral blood leukocytes. ILT7 transcripts are minimally detectable in most human tissues, but are moderately enriched in lymphoid organs, where pDCs reside. Without being bound by theory, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are useful for Petition 870250083106, dated 09 / 15 / 2025, p. 166 / 354 16 / 171 reduce pDC activities by NK / neutrophil-mediated ADCC (antibody-dependent cellular cytotoxicity) and / or macrophage-mediated ADCP (antibody-dependent cellular phagocytosis) and are therefore useful, for example, in the treatment and prevention of autoimmune diseases.

[0063] Before further describing this disclosure, it should be understood that the disclosure is not limited to the specific modalities set forth, and it should also be understood that the terminology used in this document is intended to describe specific modalities and is not intended to be limiting. A. DEFINITIONS

[0064] Unless defined otherwise in this document, the scientific and technical terms used in these disclosures shall have the meanings that are commonly understood by those of ordinary skill in the state of the art. Furthermore, unless the context requires otherwise, singular terms shall include plurals and plural terms shall include the singular. Generally, the nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry and hybridization described in this document are those well known and commonly used in the art.

[0065] The term “a” or “an” entity refers to one or more of these entities; for example, “an antibody” is understood to represent one or more antibodies.

[0066] The term “and / or”, when used in this document, should be considered as a specific disclosure of each of the two specified features or components, with or without the other. Thus, the term “and / or”, as used in a phrase such as “A and / or B” in this document, is intended to include “A and B”, “A or B”, “A” (alone) and “B” (alone). Similarly, the term “and / or”, as used in a phrase such as “A, B and / or C”, is intended to encompass Petition 870250083106, dated 09 / 15 / 2025, p. 167 / 354 17 / 171 each of the following aspects: A, B and C; A, B or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0067] As used in this document, the term “about” is used to indicate that a value includes the inherent error variation for the device, the method employed to determine the value, or the variation that exists between individuals in the study. The term “about” encompasses the exact number quoted. In some embodiments, “about” means within plus or minus 10% of a given value or range. In certain embodiments, “about” means that the variation is ±5%, ±4%, ±3%, ±2%, ±1%, ±0.5%, ±0.2%, or ±0.1% of the value to which “about” refers. In some embodiments, “about” means that the variation is ±1%, ±0.5%, ±0.2%, or ±0.1% of the value to which “about” refers.

[0068] The term “antibody” and its grammatical equivalents, as used in this document, refer to an immunoglobulin molecule that specifically recognizes and binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or a combination of any of the foregoing, through at least one antigen-binding site, wherein the antigen-binding site is generally within the variable region of the immunoglobulin molecule.As used in this document, the term encompasses intact polyclonal antibodies, intact monoclonal antibodies, single-domain antibodies (sdAbs; e.g., camelid antibodies, alpaca antibodies), single-chain Fv antibodies (scFv), heavy-chain antibodies (HCAbs), light-chain antibodies (LCAbs), multispecific antibodies, bispecific antibodies, monospecific antibodies, monovalent antibodies, and any other modified immunoglobulin molecule comprising an antigen-binding site (e.g., double variable domain immunoglobulin molecules), provided the antibodies exhibit the desired biological activity. Antibodies also include, but are not limited to, mouse antibodies, camel antibodies, chimeric antibodies, humanized antibodies, and human antibodies. Petition 870250083106, dated 09 / 15 / 2025, pp. 168 / 354 18 / 171 An antibody can be any of the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), based on the identity of their constant heavy chain domains, termed alpha, delta, epsilon, gamma, and mu, respectively. Unless expressly stated otherwise, the term “antibody,” as used in this document, includes an “antigen-binding fragment” of intact antibodies. The term “antigen-binding fragment,” as used in this document, refers to a portion or fragment of an intact antibody that is the antigenically determinant variable region of an intact antibody.Examples of antigen-binding fragments include, but are not limited to, Fab, Fab', F(ab')2, Fv, linear antibodies, single-chain antibody molecules (e.g., scFv), heavy chain antibodies (HCAbs), light chain antibodies (LCAbs), disulfide-linked scFv (dsscFv), diabodies, tribobodies, tetrabodies, minibodies, double variable domain (DVD) antibodies, single variable domain (sdAbs; e.g., camelid antibodies, alpaca antibodies), and single variable domain heavy chain (VHH) antibodies, and bispecific or multispecific antibodies formed from antibody fragments. A “bispecific” antibody is an artificial hybrid antibody that possesses two different antigen-binding sites, which specifically recognize and bind to two different targets. Bispecific antibodies can be produced by a variety of methods, including hybridoma fusion or Fab' fragment ligation.See, for example, Songsivilai & Lachmann, Clin. Exp. Immunol. 79:315-321 (1990); Kostelny et al., J. Immunol. 148, 1547-1553 (1992).

[0069] The term “humanized antibody,” as used in this document, refers to forms of non-human antibodies (e.g., murine) that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof containing minimal non-human sequences. Typically, humanized antibodies are human immunoglobulins. In some cases, residues of the Fv structural region of an immunoglobulin Petition 870250083106, dated 09 / 15 / 2025, page 169 / 354 19 / 171 human CDRs are replaced by corresponding residues in an antibody from a non-human species. In some cases, CDR residues are replaced by CDR residues from a non-human species (e.g., mouse, rat, hamster, camel) that have the desired specificity, affinity, and / or binding capacity. The humanized antibody can be further modified by replacing additional residues in the Fv structural region and / or within the replaced non-human residues to refine and optimize the antibody's specificity, affinity, and / or binding capacity. The term "human antibody," as used in this document, refers to an antibody produced by a human being or an antibody with an amino acid sequence corresponding to an antibody produced by a human being, made using any of the techniques known in the art.

[0070] The term “heavy chain,” when used in reference to an antibody, refers to a polypeptide chain of approximately 50–70 kDa, in which the amino-terminal portion includes a variable region of about 120 to 130 or more amino acids and a carboxyl-terminal portion that includes a constant region. The constant region can be of one of five distinct types, called alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the constant region of the heavy chain. The distinct heavy chains differ in size: α, δ, and γ contain approximately 450 amino acids, while μ and ε contain approximately 550 amino acids. When combined with a light chain, these distinct types of heavy chains give rise to five well-known classes of antibodies, IgA, IgD, IgE, IgG, and IgM, respectively, including four IgG subclasses, namely IgG1, IgG2, IgG3, and IgG4. A heavy chain can be a human heavy chain.

[0071] The term “light chain”, when used in reference to an antibody, refers to a polypeptide chain of approximately 25 kDa, in which the amino-terminal portion includes a variable region of approximately 100 to approximately 110 or more amino acids and a carboxyl-terminal portion that includes a region Petition 870250083106, dated 09 / 15 / 2025, p. 170 / 354 20 / 171 constant. The approximate length of a light chain is 211 to 217 amino acids. There are two distinct types, called kappa (κ) and lambda (λ), based on the amino acid sequence of the constant domains. The amino acid sequences of the light chain are well known in the state of the art. A light chain can be a human light chain.

[0072] The term “variable domain” or “variable region” refers to a portion of the light or heavy chains of an antibody that is generally located at the amino terminus of the light or heavy chain and has a length of about 120 to 130 amino acids in the heavy chain and about 100 to 110 amino acids in the light chain, and are used in the binding and specificity of each particular antibody to its particular antigen. Variable domains differ extensively in sequence between different antibodies. Variability in sequence is concentrated in the CDRs, while the less variable portions in the variable domain are called structure regions (FRs). The CDRs of the light and heavy chains are primarily responsible for the interaction of the antibody with the antigen. The numbering of amino acid positions used in this document is in accordance with the EU Index, as in Kabat et al. (1991) Sequences of proteins of immunological interest.(U.S. Department of Health and Human Services, Washington, DC) 5th ed. A variable region can be a human variable region.

[0073] A CDR refers to one of three hypervariable regions (H1, H2, or H3) within the non-structural region of the VH β-sheet structure of the immunoglobulin (Ig or antibody), or one of three hypervariable regions (L1, L2, or L3) within the non-structural region of the VL β-sheet structure of the antibody. Consequently, CDRs are sequences of variable regions interspersed within the structure region sequences. CDR regions are well known to experts in the field and have been defined by a variety of methods / systems. These systems and / or definitions have been developed and refined over the years and include Kabat, Chothia, IMGT, AbM, and Contact. For example, Kabat defines the regions of greatest hypervariability within the Petition 870250083106, dated 09 / 15 / 2025, page 171 / 354 21 / 171 antibody variable domains (V) (Kabat et al, J. Biol. Chem. 252:6609-6616 (1977); Kabat, Adv. Prot. Chem. 32: 1-75 (1978)). The Chothia definition is based on the location of structural loop regions, which defines CDR region sequences as those residues that are not part of the conserved β-sheet structure and are therefore capable of adapting to different conformations (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terminologies are well recognized in the state of the art. Furthermore, the IMGT system is based on sequence variability and the location within the structure of variable regions. The AbM definition is a compromise between Kabat and Chothia. The contact definition is based on analyses of available antibody crystal structures. Software programs (e.g., abYsis) are available and known to those knowledgeable in the field for antibody sequence analysis and CDR determination.The positions of CDRs within a canonical antibody variable domain have been determined by comparing numerous structures (Al-Lazikani et al., J. Mol. Biol. 273:927-948 (1997); Morea et al., Methods 20:267-279 (2000)). Because the number of residues within a hypervariable region varies in different antibodies, additional residues relative to the canonical positions are conventionally numbered a, b, c, and so on alongside the residue number in the canonical variable domain numbering scheme (Al-Lazikani et al., supra (1997)). This nomenclature is equally well known to those skilled in the art.

[0074] For example, the CDRs defined according to the Kabat (hypervariable) or Chothia (structural) designations are presented in the table below.

[0075] Table 1A. Kabat1 Chothia2 Loop Location VHCDR1 31-35 26-32 connecting chains B and C VHCDR2 50-65 53-55 connecting chains C and C VHCDR3 95-102 96-101 connecting chains F and G VLCDR1 24-34 26-32 connecting chains B and C Petition 870250083106, dated 09 / 15 / 2025, page 172 / 354 22 / 171 VLCDR2 50-56 50-52 linking chains C and C VLCDR3 89-97 91-96 linking chains F and G 1 The numbering of the residues follows the nomenclature of Kabat et al., supra 2A. The numbering of the residues follows the nomenclature of Chothia et al., supra.

[0076] One or more CDRs can also be incorporated into a molecule covalently or non-covalently to make it an immunoadhesin. An immunoadhesin can incorporate the CDR(s) as part of a larger polypeptide chain, can covalently link the CDR(s) to another polypeptide chain, or can incorporate the CDR(s) non-covalently. CDRs allow the immunoadhesin to bind to a specific antigen of interest. CDR regions can be analyzed, for example, by the abysis website (abysis.org).

[0077] The terms “epitope” and “antigenic determinant” are used interchangeably in this document and refer to the site on the surface of a targeting molecule to which an antibody or antigen-binding fragment binds, such as a region located on the surface of an antigen. The targeting molecule may comprise a protein, a peptide, a nucleic acid, a carbohydrate, or a lipid. An epitope with immunogenic activity is a portion of a targeting molecule that elicits an immune response in an animal. An epitope of a targeting molecule with antigenic activity is a portion of the targeting molecule to which an antibody binds, as determined by any method well known in the art, including, for example, by an immunoassay. Antigenic epitopes do not necessarily have to be immunogenic.Epitopes generally consist of clusters of chemically active molecules, such as amino acids or sugar side chains, and have specific three-dimensional structural features as well as specific charge characteristics. The term "epitope" includes both linear and conformational epitopes. A region of a targeting molecule (e.g., a polypeptide) that contributes to an epitope may be composed of... Petition 870250083106, dated 09 / 15 / 2025, page 173 / 354 23 / 171 contiguous amino acids of the polypeptide, or the epitope, can originate from two or more non-contiguous regions of the targeting molecule. The epitope may or may not be a three-dimensional surface feature of the targeting molecule. Epitopes formed from contiguous amino acids (also called linear epitopes) are typically retained after protein denaturation, while epitopes formed by tertiary folding (also called conformational epitopes) are typically lost after protein denaturation. An epitope typically includes at least 3, and more commonly, at least 5, 6, 7, or 8-10 amino acids in a unique spatial conformation.

[0078] The term “specifically binds,” as used in this document, means that a polypeptide or molecule interacts more frequently, more rapidly, for a longer duration, with greater affinity, or with some combination of the above, with the epitope, protein, or targeting molecule than with alternative substances, including related and unrelated proteins. A binding fraction (e.g., antibody) that specifically binds to a targeting molecule (e.g., antigen) can be identified, for example, by immunoassays, ELISAs, biolayer interferometry (“BLI”), SPR (e.g., Biacore), or other techniques known to those skilled in the art. Typically, a specific reaction will be at least twice as large as the background signal or noise and may be more than 10 times larger than the background. See, for example, Paul, ed., 1989, Fundamental Immunology Second Edition, Raven Press, New York, on pages 332-336 for a discussion on antibody specificity. A binding fraction that binds specifically to a targeting molecule may bind to the targeting molecule with a greater affinity than its affinity for a different molecule. In some embodiments, a binding fraction that binds specifically to a targeting molecule may bind to the targeting molecule with an affinity that is at least 20 times greater, at least 30 times greater, by. Petition 870250083106, dated 09 / 15 / 2025, pp. 174 / 354 24 / 171 less than 40 times greater, at least 50 times greater, at least 60 times greater, at least 70 times greater, at least 80 times greater, at least 90 times greater, or at least 100 times greater than its affinity for a different molecule. In some embodiments, a binding fraction that specifically binds to a specific targeting molecule binds to a different molecule with such low affinity that the binding cannot be detected using an assay described in this document or known in the art. In some embodiments, “specifically binds” means, for example, that a binding fraction binds to a targeting molecule with a Kd of about 0.1 mM or less. In some embodiments, “specifically binds” means that a polypeptide or molecule binds to a target with a Kd of about 10 μM or less or about 1 μM or less.In some embodiments, “specific binding” means that a polypeptide or molecule binds to a target with a Kd of about 0.1 μM or less, about 0.01 μM or less, or about 1 nM or less. Due to sequence identity between homologous proteins in different species, specific binding may include a polypeptide or molecule that recognizes a protein or target in more than one species. Similarly, due to homology within certain regions of polypeptide sequences of different proteins, specific binding may include a polypeptide or molecule that recognizes more than one protein or target. It is understood that, in some embodiments, a binding fraction (e.g., antibody) that specifically binds to a first target may or may not specifically bind to a second target. Thus, “specific binding” does not necessarily require (although it may include) exclusive binding, i.e., binding to a single target.Thus, a binding fraction (e.g., antibody) can, in some embodiments, bind specifically to more than one target. For example, an antibody may, in certain cases, comprise two identical antigen-binding sites, each of which binds specifically to the same epitope on two or more proteins. In certain alternative embodiments,... Petition 870250083106, dated 09 / 15 / 2025, pp. 175 / 354 25 / 171 an antibody can be bispecific and comprise at least two antigen-binding sites with different specificities.

[0079] The term “binding affinity,” as used in this document, generally refers to the strength of the sum total of non-covalent interactions between a binding fraction and a targeting molecule (e.g., antigen). The binding of a binding fraction and a targeting molecule is a reversible process, and the binding affinity is normally reported as an equilibrium dissociation constant (Kd). Kd is the ratio of the dissociation rate (koff or kd) to the association rate (kon or ka). The smaller the Kd of a binding pair, the greater the affinity. A variety of methods for measuring binding affinity are known in the art, any of which can be used for purposes of this disclosure. Specific illustrative examples include the following. In some embodiments, the “Kd” or “Kd value” can be measured by assays known in the art, for example, by a binding assay.Kd can be measured in a radiolabeled antigen binding assay (RIA) (Chen, et al., (1999) J. MolBiol293:865881). The Kd or Kd value can also be measured using biolayer interferometry (BLI) using, for example, the Gator system (Probe Life) or the Octet-96 system (Sartorius AG). The Kd or Kd value can also be measured using surface plasmon resonance (SPR) assays from Biacore, using, for example, a BIAcore™-2000 or a BIAcore™-3000 (BIAcore, Inc., Piscataway, NJ). Binding affinity can also be quantified with EC50, which is the ligand concentration at which half of the target is present in the bound state in a binding assay.

[0080] The terms “polypeptide”, “peptide”, “protein” and their grammatical equivalents, as used interchangeably in this document, refer to polymers of amino acids of any length, which may be linear or branched. It may include unnatural or modified amino acids or be interrupted by non-amino acids. A polypeptide, peptide or protein may also be modified by, for example, the formation of... Petition 870250083106, dated 09 / 15 / 2025, page 176 / 354 26 / 171 disulfide bond, glycosylation, lipidation, acetylation, phosphorylation or any other manipulation or modification.

[0081] The term “variant,” as used in this document, in relation to a protein or polypeptide with specific sequence characteristics (the “reference protein” or “reference polypeptide”), refers to a different protein or polypeptide that has one or more (for example, about 1 to about 30, about 1 to about 25, about 1 to about 20, about 1 to about 15, about 1 to about 10, or about 1 to about 5) amino acid substitutions, deletions, and / or additions compared to the reference protein or reference polypeptide. Changes in an amino acid sequence may be amino acid substitutions. Changes in an amino acid sequence may be conservative amino acid substitutions. Changes in an amino acid sequence may be amino acid deletions. A variant may be a fragment of the reference protein or polypeptide.A functional variant of a protein or polypeptide retains the basic structural and functional properties of the reference protein or polypeptide.

[0082] The terms “polynucleotide,” “nucleic acid,” and their grammatical equivalents, as used interchangeably in this document, refer to a polymer or oligomer of nucleotides of any length. Nucleotides may be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases (such as methylated, hydroxymethylated, or glycosylated), non-natural nucleotides, non-nucleotide building blocks that exhibit structure and / or function similar to natural nucleotides (i.e., “nucleotide analogs”), and / or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. Nucleic acids or polynucleotides may be heterogeneous or homogeneous in composition, may be isolated from natural sources, or may be produced artificially or synthetically. Furthermore, nucleic acids may be DNA or RNA, or a mixture thereof, and may exist Petition 870250083106, dated 09 / 15 / 2025, page 177 / 354 27 / 171 permanently or transitionally in single- or double-stranded form, including homoduplex, heteroduplex, and hybrid states. Nucleic acid structures also include, for example, a DNA / RNA helix, peptide nucleic acid (PNA), morpholino nucleic acid (see, for example, Braasch and Corey, Biochemistry, 4(14): 4503-4510 (2002) and U.S. Patent 5,034,506), locked nucleic acid (LNA; see Wahlestedt et al., Proc. Natl. Acad. Sci. USA, 97: 5633-5638 (2000)), cyclohexenyl nucleic acids (see Wang, Am. Chem. Soc., 122: 8595-8602 (2000)), and / or a ribozyme.

[0083] The terms “identical,” percent “identity,” and their grammatical equivalents, as used in this document in the context of two or more polynucleotides or polypeptides, refer to two or more sequences or subsequences that are identical or have a specified percent of nucleotides or amino acid residues that are identical when compared and aligned (introducing gaps, if necessary) to maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. Percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Several algorithms and software that can be used to obtain amino acid or nucleotide sequence alignments are well known in the art. This includes, but is not limited to, BLAST, ALIGN, Megalign, BestFit, GCG Wisconsin Package, and variants thereof.In some embodiments, two polynucleotides or polypeptides provided in this document are substantially identical, meaning that they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% nucleotide or amino acid residue identity when compared and aligned for maximum match, as measured using a sequence comparison algorithm or by visual inspection. In some embodiments, identity exists in a region of the amino acid sequences. Petition 870250083106, dated 09 / 15 / 2025, page 178 / 354 28 / 171 that has at least about 10 residues, at least about 20 residues, at least about 40-60 residues, at least about 60-80 residues in length, or any integer value between them. In some embodiments, identity exists in a region larger than 60-80 residues, such as at least about 80-100 residues, and in some embodiments the sequences are substantially identical throughout the length of the sequences being compared, such as the coding region of a target protein or antibody. In some embodiments, identity exists in a region of the nucleotide sequences that has at least about 10 bases, at least about 20 bases, at least about 40-60 bases, at least about 60-80 bases in length, or any integer value between them.In some embodiments, the identity exists in a region larger than 60-80 bases, such as at least about 80-1000 bases or more, and in some embodiments the sequences are substantially identical throughout the length of the sequences being compared, such as a nucleotide sequence encoding a protein of interest.

[0084] The term “vector” and its grammatical equivalents, as used in this document, refer to a vehicle used to transport genetic material (e.g., a polynucleotide sequence) that can be introduced into a host cell, where it can be replicated and / or expressed. Applicable vectors for use include, for example, expression vectors, plasmids, phage vectors, viral vectors, episomes, and artificial chromosomes, which may include selection sequences or operable markers for stable integration into the chromosome of a host cell. In addition, vectors may include one or more selectable marker genes and appropriate expression control sequences. Selectable marker genes that may be included, for example, provide resistance to antibiotics or toxins, complement auxotrophic deficiencies, or provide essential nutrients that are not in the culture medium.Expression control sequences may include constitutive and inducible promoters. Petition 870250083106, dated 09 / 15 / 2025, p. 179 / 354 29 / 171 transcription enhancers, transcription terminators, and the like, which are well known in the art. When two or more polynucleotides are to be co-expressed, both polynucleotides can be inserted, for example, into a single expression vector or into separate expression vectors. For single-vector expression, the coding polynucleotides can be operationally linked to a common expression control sequence or linked to different expression control sequences, such as an inducible promoter and a constitutive promoter. The introduction of polynucleotides into a host cell can be confirmed using methods well known in the art.It is understood by those skilled in the art that polynucleotides are expressed in sufficient quantity to produce a desired product (e.g., an anti-ILT7 antibody or antigen-binding fragment, as described in this document), and it is further understood that expression levels can be optimized to achieve sufficient expression using methods well known in the art.

[0085] As used in this document, the term “encode” and its grammatical equivalents refer to the inherent property of specific nucleotide sequences in a polynucleotide or nucleic acid, such as a gene, cDNA, or mRNA, to serve as templates for the synthesis of other polymers and macromolecules in biological processes having a defined nucleotide sequence (i.e., rRNA, tRNA, and mRNA) or a defined amino acid sequence and the resulting biological properties. Thus, a gene encodes a protein if the transcription and translation of the mRNA corresponding to that gene produce the protein. Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. Protein-encoding and RNA-encoding nucleotide sequences may include introns. Petition 870250083106, dated 09 / 15 / 2025, pp. 180 / 354 30 / 171

[0086] A polypeptide, peptide, protein, antibody, polynucleotide, vector, cell, or composition that is “isolated” is a polypeptide, peptide, protein, antibody, polynucleotide, vector, cell, or composition that is in a form not found in nature. Isolated polypeptides, peptides, proteins, antibodies, polynucleotides, vectors, cells, or compositions include those that have been purified to a degree where they are no longer in a form in which they are found in nature. In some embodiments, an isolated polypeptide, peptide, protein, antibody, polynucleotide, vector, cell, or composition is substantially pure.

[0087] The term “treat” and its grammatical equivalents, as used in this document in connection with a disease or condition, or an individual who has a disease or condition, refer to an action that suppresses, eliminates, reduces and / or improves a symptom, the severity of the symptom and / or the frequency of the symptom associated with the disease or disorder being treated.

[0088] The term “administer” and its grammatical equivalents, as used in this document, refer to the act of administering, or causing to be administered, a therapeutic or pharmaceutical composition to the body of an individual by a method described in this document or otherwise known in the art. The therapeutic agent may be a compound, a polypeptide, an antibody, a cell, or a population of cells. The administration of a therapeutic or pharmaceutical composition includes the prescription of a therapeutic or pharmaceutical composition to be administered into the body of an individual. Exemplary forms of administration include oral dosage forms, such as tablets, capsules, syrups, suspensions; injectable dosage forms, such as intravenous (IV), intramuscular (IM), or intraperitoneal (IP); transdermal dosage forms, including creams, gels, powders, or patches; buccal dosage forms; powders for inhalation, sprays, suspensions, and rectal suppositories.

[0089] The terms “effective quantity”, “therapeutically effective quantity” and their grammatical equivalents, as used Petition 870250083106, dated 09 / 15 / 2025, pp. 181 / 354 31 / 171 in this document refers to the administration of an agent to an individual, alone or as part of a pharmaceutical composition and in a single dose or as part of a series of doses, in an amount capable of having any detectable positive effect on any symptom, aspect or feature of a disease, disorder or condition when administered to the individual. The therapeutically effective amount can be determined by measuring the relevant physiological effects. The exact amount needed varies from individual to individual, depending on the individual's age, weight and general condition, the severity of the condition being treated, the clinician's judgment, and so forth. An appropriate “effective amount” in any individual case can be determined by someone with normal skill in the field using routine experimentation.

[0090] The term “pharmaceutically acceptable vehicle” or “pharmaceutically acceptable excipient” refers to a material that is suitable for administering a drug to an individual along with an active agent, without causing undesirable biological effects or interacting in a harmful way with any other components of the pharmaceutical composition.

[0091] The term “subject,” as used in this document, refers to any animal (e.g., a mammal), including but not limited to humans, non-human primates, canines, felines, rodents, and the like, that is to be the recipient of a specific treatment. The individual may be a mammal. An individual may have a specific disease or condition.

[0092] Intervals: Throughout this disclosure, various aspects of the invention may be presented in interval format. It should be understood that the interval description is merely for convenience and brevity and should not be interpreted as an inflexible limitation to the scope of the invention. Consequently, the description of an interval should be considered as having specifically disclosed all possible subintervals, as well as individual numerical values ​​within that interval. Petition 870250083106, dated 09 / 15 / 2025, page 182 / 354 32 / 171 interval. For example, the description of an interval as 1 to 6 should be considered as having specifically disclosed subintervals, such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numbers within that interval, for example, 1, 2, 2, 7, 3, 4, 5, 5, 3 and 6. This applies regardless of the width of the interval.

[0093] Exemplary genes and polypeptides are described in this document with reference to GenBank numbers, GI numbers and / or SEQ ID NOs. It is understood that a specialist in the field can easily identify homologous sequences by reference to sequence sources, including but not limited to GenBank (ncbi.nlm.nih.gov / genbank / ) and EMBL (embl.org / ). B. Anti-ILT7 Antibodies and Fragments of ANTIGEN BINDING

[0094] Antibodies or antigen-binding fragments that specifically bind to ILT7 (e.g., human ILT7) are provided in this document. In some embodiments, anti-ILT7 antibodies are provided in this document. In some embodiments, the antibody is an IgA, IgD, IgE, IgG, or IgM antibody. In some embodiments, the antibody is an IgA antibody. In some embodiments, the antibody is an IgD antibody. In some embodiments, the antibody is an IgE antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the antibody is an IgM antibody. In some embodiments, the antibodies provided in this document may be an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the antibody is an IgG1 antibody. In some embodiments, the antibody is an IgG2 antibody. In some embodiments, the antibody is an IgG3 antibody. In some embodiments, the antibody is an IgG4 antibody.

[0095] In some embodiments, antigen-binding fragments of an anti-ILT7 antibody are provided in this document. In some embodiments, the antigen-binding fragments provided in this document may be a single-domain antibody (sdAb), an antibody of Petition 870250083106, dated 09 / 15 / 2025, pp. 183 / 354 33 / 171 heavy chain (HCAb), a Fab, a Fab', an F(ab')2, an Fv, a single-chain variable fragment (scFv) or a (scFv)2. In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is a single-domain antibody (sdAb). In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is a heavy chain antibody (HCAb). In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is a Fab. In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is a Fab'. In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is an F(ab')2. In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is an Fv. In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is an scFv. In some embodiments, the antigen-binding fragment of an anti-ILT7 antibody is a disulfide-linked scFv [(scFv)2].In some forms, the antigen-binding fragment of an anti-ILT7 antibody is a diabody (dAb).

[0096] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise recombinant antibodies or antigen-binding fragments. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise monoclonal antibodies or antigen-binding fragments. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise polyclonal antibodies or antigen-binding fragments. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise camelid antibodies or antigen-binding fragments (e.g., camels, dromedaries, and llamas). In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise chimeric antibodies or antigen-binding fragments.In some embodiments, anti-ILT7 antibodies or antigen-binding fragments are provided herein. Petition 870250083106, dated 09 / 15 / 2025, pp. 184 / 354 34 / 171 document comprises humanized antibodies or antigen-binding fragments. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise human antibodies or antigen-binding fragments. In some embodiments, human anti-ILT7 scFvs are provided in this document.

[0097] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are isolated. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document are substantially pure.

[0098] In some embodiments, the anti-ILT7 antibody or antigen-binding fragment provided in this document comprises a multispecific antibody or antigen-binding fragment. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment provided in this document comprises a bispecific antibody or antigen-binding fragment. In some embodiments, the bispecific antibody or antigen-binding fragment comprises an anti-ILT7 antibody or antigen-binding fragment provided in this document. In some embodiments, the bispecific antibody or antigen-binding fragment comprises an anti-ILT7 scFv provided in this document.

[0099] In some embodiments, the anti-ILT7 antibody or antigen-binding fragment provided in this document comprises a monovalent antigen-binding site. In some embodiments, an anti-ILT7 antibody or antigen-binding fragment comprises a monospecific binding site. In some embodiments, an anti-ILT7 antibody or antigen-binding fragment comprises a bivalent binding site.

[00100] In some embodiments, an anti-ILT7 antibody or antigen-binding fragment is a monoclonal antibody or antigen-binding fragment. Monoclonal antibodies can be prepared by any method known to experts in the field. An exemplary approach is screening protein expression libraries, for example, Petition 870250083106, dated 09 / 15 / 2025, pp. 185 / 354 35 / 171 phage or ribosome display libraries. Phage display is described, for example, in Ladner et al., US Patent No. 5,223,409; Smith (1985) Science 228:1315-1317; and WO 92 / 18619. In some embodiments, recombinant monoclonal antibodies are isolated from phage display libraries expressing variable regions or CDRs of a desired species. Screening of phage libraries can be performed by several techniques known in the art.

[00101] In some embodiments, a monoclonal antibody is modified using recombinant DNA technology to generate alternative antibodies. In some embodiments, the constant domains of the light and heavy chains of a mouse monoclonal antibody are replaced by the constant regions of a human antibody to generate a chimeric antibody. In some embodiments, the constant regions are truncated or removed to generate a desired antibody fragment from a monoclonal antibody. In some embodiments, site-directed or high-density mutagenesis of the variable region(s) is used to optimize the specificity and / or affinity of a monoclonal antibody.

[00102] In some embodiments, the anti-ILT7 Ab12 antibody clone is provided in this document. The sequence features are described below. The specific CDR sequences defined in this document are generally based on the Kabat or Chothia definition. However, it is understood that a general reference to one or more heavy chain CDRs and / or one or more light chain CDRs of a specific antibody encompasses all CDR definitions known to those skilled in the art.

[00103] Table 1B Amino acid sequences of variable region light chain CDRs (VL CDRs) of Ab12 VL CDR1 VL CDR2 VL CDR3 Kabat RASQSVSTSSYSYMH (SEQ ID NO: 11) YASNLES (SEQ ID NO: 12) QHSWDIPYT (SEQ ID NO: 13) Chothia RASQSVSTSSYSYMH (SEQ ID NO: 11) YASNLES (SEQ ID NO: 12) QHSWDIPYT (SEQ ID NO: 13) Petition 870250083106, dated 09 / 15 / 2025, page 186 / 354 36 / 171

[00104] Table 2 Amino acid sequences of variable heavy chain region CDRs (VH CDRs) of Ab12 Sequence VH CDR1 VH CDR2 VH CDR3 Kabat EYPMH (SEQ ID NO: 14) MIYTDTGEPAYAEEF KG (SEQ ID NO: 15) ELGQNFDY (SEQ ID NO: 16) Chothia GYTFTEY (SEQ ID NO: 17) YTDTGE (SEQ ID NO: 18) ELGQNFDY (SEQ ID NO: 16)

[00105] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise one, two, three, four, five, and / or six CDRs of any of the antibodies described in this document. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise a variable light chain (VL) region comprising one, two, and / or three light chain CDRs (VL CDRs) from Table 1B. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise a variable heavy chain (VH) region comprising one, two, and / or three heavy chain CDRs (VH CDRs) from Table 2. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments provided in this document comprise one, two, and / or three VL CDRs from Table 1B and one, two, and / or three VH CDRs from Table 2.

[00106] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising a VL comprising (1) a VL CDR1 with the amino acid sequence of SEQ ID NO: 11; (2) a VL CDR2 with the amino acid sequence of SEQ ID NO: 12; and / or (3) a VL CDR3 with the amino acid sequence of SEQ ID NO: 13; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in VL CDRs; and / or a VH comprising (1) a VL CDR1 having an amino acid sequence Petition 870250083106, dated 09 / 15 / 2025, pp. 187 / 354 37 / 171 selected from the group consisting of SEQ ID NO: 14 or 17; (2) a CDR2 VH with the amino acid sequence of SEQ ID NO: 15 or 18; and / or (3) a CDR3 VH with the amino acid sequence of SEQ ID NO: 16; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in CDRs VH.

[00107] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL comprising (1) a VL CDR1 with the amino acid sequence of SEQ ID NO: 11; (2) a VL CDR2 with the amino acid sequence of SEQ ID NO: 12; or (3) a VL CDR3 with the amino acid sequence of SEQ ID NO: 13; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in the VL CDR. In some embodiments, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in the VL CDR.In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL comprising (1) a VL CDR1 with the amino acid sequence of SEQ ID NO: 11; (2) a VL CDR2 with the amino acid sequence of SEQ ID NO: 12; and (3) a VL CDR3 with the amino acid sequence of SEQ ID NO: 13; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in CDR VLs. In some embodiments, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in CDR VLs.

[00108] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 with a VL are provided in this document, wherein VL comprises VL CDR1, CDR2 and CDR3 with the amino acid sequences of SEQ ID NOS: 11, 12 and 13, respectively, as defined by Kabat; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 Petition 870250083106, dated 09 / 15 / 2025, pp. 188 / 354 38 / 171 amino acid substitutions, additions, and / or deletions in VL CDRs. In some embodiments, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in the VL CDRs. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 with a VL are provided in this document, wherein the VL comprises VL CDR1, CDR2, and CDR3 with the amino acid sequences of the SEQ ID NOs: 11, 12, and 13, respectively, as defined by Chothia; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in VL CDRs. In some embodiments, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in the VL CDRs.

[00109] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document comprising a VH comprising (1) a CDR1 VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 14 or 17; (2) a CDR2 VH with the amino acid sequence of SEQ ID NO: 15 or 18; or (3) a CDR3 VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 16; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in the CDR VH. In some embodiments, the variant has up to about 5 amino acid substitutions, additions and / or deletions in the CDR VH.In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document comprising a VH comprising (1) a CDR1 VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 14 or 17; (2) a CDR2 VH having the amino acid sequence of SEQ ID NO: 15 or 18; and (3) a CDR3 VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 16; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in VH. Petition 870250083106, dated 09 / 15 / 2025, pp. 189 / 354 39 / 171 CDRs. In some forms, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in the VH CDRs.

[00110] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 with a VH are provided in this document, wherein the VH comprises VH CDR1, CDR2, and CDR3 with the amino acid sequences of SEQ ID NOs: 14, 15, and 16, respectively, as defined by Kabat; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in the VH CDRs. In some embodiments, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in the VH CDRs.In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 with a VH are provided in this document, wherein the VH comprises VH CDR1, CDR2, and CDR3 with the amino acid sequences of the SEQ ID NOs: 17, 18, and 16, respectively; as defined by Chothia; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in the VH CDRs. In some embodiments, the variant has up to about 5 amino acid substitutions, additions, and / or deletions in the VH CDRs.

[00111] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising, as defined by Kabat, (a) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in VL CDRs; and / or (b) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; or a variant thereof having up to about 3, about 5, about 8, about 10, Petition 870250083106, dated 09 / 15 / 2025, pp. 190 / 354 40 / 171 approximately 12 or approximately 15 substitutions, additions and / or deletions of amino acids in VH CDRs.

[00112] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and VH CDR3 are provided in this document, having the amino acid sequences of the SEQ ID NOs: 11, 12, 13, 14, 15 and 16, respectively, as defined by Kabat, or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in CDRs.

[00113] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 with a VL are provided in this document, wherein the VL comprises VL CDR1, VL CDR2 and VL CDR3 with the amino acid sequences of the SEQ ID NOS: 11, 12 and 13, respectively; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in VL CDRs; and / or (b) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of the NOS: 17, 18 and 16, respectively; or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in the VH CDRs.

[00114] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and VH CDR3 are provided in this document, having the amino acid sequences of SEQ ID NOs: 11, 12, 13, 17, 18 and 16, respectively, as defined by Chothia, or a variant thereof having up to about 3, about 5, about 8, about 10, about 12 or about 15 amino acid substitutions, additions and / or deletions in the CDRs. Petition 870250083106, dated 09 / 15 / 2025, pp. 191 / 354 41 / 171

[00115] Table 3A Amino acid sequences of the variable region of the light chain (VL) and the variable region of the heavy chain (VH) of the chimeric antibody Ab12 (cmAb12) and humanized VLs (hu-VL) and VHs (hu-VH). Domínio Ab Sequência cmAb12 VL DIVLTQSPASLAVSLGQRATISCRASQSVSTSSYSYMHWYQ QKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLNIHPVE EEDTATYYCQHSWDIPYTFGGGTKLEIK (SEQ ID NO: 9) cmAb12 VH QIQLVQSGPELKKPGETVKISCKASGYTFTEYPMHWVKQAP GKGFKWMGMIYTDTGEPAYAEEFKGRFAFSLETSASTAYLQI NNLKNEDTATYFCVRELGQNFDYWGQGTTLTVSS (SEQ ID NO: 10) Hu-VL1 DIVLTQSPASLAVSPGQRATITCRASQSVSTSSYSYMHWYQ QKPGQPPKLLIYYASNLESGVPARFSGSGSGTDFTLTINPVE AEDTANYYCQHSWDIPYTFGQGTKLEIK (SEQ ID NO: 19) Hu-VL2 DIVLTQSPASLAVSPGQRATITCRASQSVSTSSYSYMHWYQ QKPGQPPKLLIKYASNLESGVPARFSGSGSGTDFTLTINPVE ANDTANYYCQHSWDIPYTFGQGTKLEIK (SEQ ID NO: 20) Hu-VL3 DIVMTQSPDSLAVSLGERATINCRASQSVSTSSYSYMHWYQ QKPGQPPKLLIYYASNLESGVPDRFSGSGSGTDFTLTISSLQ AEDVAVYYCQHSWDIPYTFGQGTKLEIK (SEQ ID NO: 21) Hu-VL4 DIVLTQSPDSLAVSLGERATINCRASQSVSTSSYSYMHWYQ QKPGQPPKLLIKYASNLESGVPDRFSGSGSGTDFTLTISSLQ AEDVAVYYCQHSWDIPYTFGQGTKLEIK (SEQ ID NO: 22) Hu-VH1 QVQLVQSGSELKKPGASVKVSCKASGYTFTEYPMHWVRQA PGQGLEWMGMIYTDTGEPAYAEEFKGRFVFSLDTSVSTAYL QISSLKAEDTAVYYCARELGQNFDYWGQGTTVTVSS (SEQ ID NO: 23)Hu-VH2 QVQLVQSGSELKKPGASVKVSCKASGYTFTEYPMHWVKQA PGQGLKWMGMIYTDTGEPAYAEEFKGRFVFSLDTSVSTAYL QISSLKAEDTAVYYCARELGQNFDYWGQGTTVTVSS (SEQ ID NO: 24) Hu-VH3 Hu-VH4 Hu-VH4 QVQLVQSGAEVKKPGASVKVSKASGYTFTEYPMHWVRQA PGQRLEWMGMIYTDTGEPAYAEEFKGRVTITRDTSASTAYM ELSSRSEDTAVYYCARELGQNFDYWGQGTTVTVSS (SEQ ID NO: 26) Hu-VH5 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEYPMHWVRQA PGQGLEWMGMIYTDTGEPAYAEEFKGRVTITLDTSASTAYM Petition: 870250083106, on September 15, 2025, page. 192 / 354 42 / 171 ELNSLRSEDTAVYYCARELGQNFDYWGQGTTVTVSS (SEQ ID NO: 27) Hu-VH6 QVQLVQSGAEVKKPGASVKVSCKASGYTFTEYPMHWVRQA PGQGLKWMGMIYTDTGEPAYAEEFKGRVTITLDTSASTAYM ELNSLRSEDTAVYYCARELGQNFDYWGQGTTVTVSS (SQ ID NO: 28) This document describes antibodies or antigen-binding fragments that specifically bind to ILT7, comprising a VL with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VH with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 10.

[00117] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising: (a) a VL having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9; and (b) a VH having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, by Petition 870250083106, dated 09 / 15 / 2025, pp. 193 / 354 43 / 171 less than 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 10. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL and a VH, wherein the VL and VH have the amino acid sequences of SEQ ID NOs: 9 and 10, respectively.

[00118] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL, wherein the VL has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 9. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VL with at least 85% sequence identity with SEQ ID NO: 9. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VL with at least 90% sequence identity with SEQ ID NO: 9. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VL with at least 95% sequence identity with SEQ ID NO: 9.In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VL with at least 98% sequence identity to SEQ ID NO: 9. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL with the amino acid sequence of SEQ ID NO: 9.

[00119] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising an HV, wherein the HV has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least Petition 870250083106, dated 09 / 15 / 2025, pp. 194 / 354 44 / 171 less than 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 10. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VH with at least 85% sequence identity with SEQ ID NO: 10. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VH with at least 90% sequence identity with SEQ ID NO: 10. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VH with at least 95% sequence identity with SEQ ID NO: 10. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment has a VH with at least 98% sequence identity with SEQ ID NO: 10.In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7, comprising a VH with the amino acid sequence SEQ ID NO: 10, are provided in this document.

[00120] In some embodiments, an anti-ILT7 antibody or its antigen-binding fragment comprises a humanized antibody or antigen-binding fragment. In some embodiments, an anti-ILT7 antibody or its antigen-binding fragment comprises a VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and / or VH CDR3 of an antibody or antigen-binding fragment described in this document. In some embodiments, an anti-ILT7 antibody or its antigen-binding fragment comprises a variant of an anti-ILT7 antibody or antigen-binding fragment described in this document. A variant of an anti-ILT7 antibody or antigen-binding fragment may comprise from one to 30 amino acid substitutions, additions and / or deletions in the anti-ILT7 antibody or antigen-binding fragment.A variant of an anti-ILT7 antibody or antigen-binding fragment may comprise from one to 25 amino acid substitutions, additions, and / or deletions in the anti-ILT7 antibody or antigen-binding fragment. In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises from one to 20 substitutions. Petition 870250083106, dated 09 / 15 / 2025, pp. 195 / 354 45 / 171 additions and / or deletions in the anti-ILT7 antibody or antigen-binding fragment. In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises from one to 15 substitutions, additions, and / or deletions in the anti-ILT7 antibody or antigen-binding fragment. In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises from one to 10 substitutions, additions, and / or deletions in the anti-ILT7 antibody or antigen-binding fragment. In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises from one to five amino acid-conserving substitutions, additions, and / or deletions in the anti-ILT7 antibody or antigen-binding fragment.In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises one to three amino acid substitutions, additions, and / or deletions in the anti-ILT7 antibody or antigen-binding fragment. In some embodiments, amino acid substitutions, additions, and / or deletions are conservative amino acid substitutions. In some embodiments, the conservative amino acid substitution(s) is / are located in a CDR of the antibody or antigen-binding fragment. In some embodiments, the conservative amino acid substitution(s) is / are not located in a CDR of the antibody or antigen-binding fragment. In some embodiments, the conservative amino acid substitution(s) is / are located in a structural region of the antibody or antigen-binding fragment.

[00121] In some embodiments, humanized antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising: (a) a VL having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22; and / or Petition 870250083106, dated 09 / 15 / 2025, pp. 196 / 354 46 / 171 (b) a VH having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 23-28.In some embodiments, the humanized antibodies or their antigen-binding fragments comprise a VL with at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 19; and a VH having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 26.

[00122] In some embodiments, humanized antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising: (a) a VL having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22, the VL also having, as defined by Kabat or Chothia, VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; and / or (b) a VH having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, Petition 870250083106, dated 09 / 15 / 2025, page 197 / 354 47 / 171 at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NOs: 23-28, the VH also having (1) as defined by Kabat, VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively, or (2) as defined by Chothia, VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively. In some embodiments, VL has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 19, the VL also having, as defined by Kabat or Chothia, VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13.respectively; and VH has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NOs: 26, VH also having (1) as defined by Kabat, VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively, or (2) as defined by Chothia, VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively.

[00123] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising a VL and a VH, wherein the VL and VH have the amino acid sequences of SEQ ID NOs: 19 and 23, respectively. In some embodiments, VL and VH have the amino acid sequences of SEQ ID NOs: 19 and 24, respectively. In some Petition 870250083106, dated 09 / 15 / 2025, pp. 198 / 354 In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 19 and 25, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 19 and 26, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 19 and 27, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 19 and 28, respectively. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL and a VH, wherein VL and VH have amino acid sequences SEQ ID NOs: 20 and 23, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 20 and 24, respectively. In some modalities, VL and VH have the amino acid sequences SEQ ID NOs: 20 and 25, respectively.In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 20 and 26, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 20 and 27, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 20 and 28, respectively. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL and a VH, wherein VL and VH have amino acid sequences SEQ ID NOs: 21 and 23, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 21 and 24, respectively. In some embodiments, VL and VH have amino acid sequences SEQ ID NOs: 21 and 25, respectively. In some modalities, VL and VH have the amino acid sequences SEQ ID NOs: 21 and 26, respectively.In some embodiments, VL and VH have the amino acid sequences SEQ ID NOs: 21 and 27, respectively. In some embodiments, VL and VH have the amino acid sequences SEQ ID NOs: 21 and 28, respectively. In some embodiments, antibodies or antigen-binding fragments that bind are provided in this document. Petition 870250083106, dated 09 / 15 / 2025, pp. 199 / 354 49 / 171 specifically ILT7, comprising a VL and a VH, wherein VL and VH have amino acid sequences with SEQ ID NOs: 22 and 23, respectively. In some embodiments, VL and VH have amino acid sequences with SEQ ID NOs: 22 and 24, respectively. In some embodiments, VL and VH have amino acid sequences with SEQ ID NOs: 22 and 25, respectively. In some embodiments, VL and VH have amino acid sequences with SEQ ID NOs: 22 and 26, respectively. In some embodiments, VL and VH have amino acid sequences with SEQ ID NOs: 22 and 27, respectively. In some embodiments, VL and VH have amino acid sequences with SEQ ID NOs: 22 and 28, respectively.

[00124] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 19. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 85% sequence identity with SEQ ID NO: 19. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 90% sequence identity with SEQ ID NO: 19. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 95% sequence identity with SEQ ID NO: 19.The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 98% sequence identity with SEQ ID NO: 19. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL with the amino acid sequence of SEQ ID NO: 19. Petition 870250083106, dated 09 / 15 / 2025, pp. 200 / 354 50 / 171

[00125] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 20. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 85% sequence identity with SEQ ID NO: 20. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 90% sequence identity with SEQ ID NO: 20. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 95% sequence identity with SEQ ID NO: 20.The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 98% sequence identity with SEQ ID NO: 20. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL with the amino acid sequence of SEQ ID NO: 20.

[00126] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 21. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 85% sequence identity with SEQ ID NO: 21. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 90% Petition 870250083106, dated 09 / 15 / 2025, pp. 201 / 354 51 / 171 sequence identity with SEQ ID NO: 21. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 95% sequence identity with SEQ ID NO: 21. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 98% sequence identity with SEQ ID NO: 21. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL with the amino acid sequence of SEQ ID NO: 21.

[00127] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 22. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 85% sequence identity with SEQ ID NO: 22. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 90% sequence identity with SEQ ID NO: 22. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 95% sequence identity with SEQ ID NO: 22.The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VL with at least 98% sequence identity with SEQ ID NO: 22. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7, comprising a VL with the amino acid sequence of SEQ ID NO: 22, are provided in this document.

[00128] In some embodiments, humanized antibodies or antigen-binding fragments thereof that bind specifically to ILT7 comprising a VH are provided in this document, wherein Petition 870250083106, dated 09 / 15 / 2025, pp. 202 / 354 52 / 171 The HV has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 23. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 85% sequence identity with SEQ ID NO: 23. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 90% sequence identity with SEQ ID NO: 23. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least less than 95% sequence identity with SEQ ID NO: 23. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 98% sequence identity with SEQ ID NO: 23.In some embodiments, humanized antibodies or antigen-binding fragments that bind specifically to ILT7, comprising a VH with the amino acid sequence SEQ ID NO: 23, are provided in this document.

[00129] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising an HV are provided in this document, wherein the HV has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 24. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 85% sequence identity with SEQ ID NO: 24. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 90% sequence identity with SEQ ID NO: 24. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 95% sequence identity with SEQ ID NO: 24.Anti-Petition antibody 870250083106, dated 09 / 15 / 2025, p. 203 / 354. 53 / 171 Humanized ILT7 or its antigen-binding fragment may have a viral load (VL) with at least 98% sequence identity with SEQ ID NO: 24. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VL with the amino acid sequence of SEQ ID NO: 24 are provided in this document.

[00130] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising an HV are provided in this document, wherein the HV has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 25. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 85% sequence identity with SEQ ID NO: 25. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 90% sequence identity with SEQ ID NO: 25. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 95% sequence identity with SEQ ID NO: 25.The humanized anti-ILT7 antibody or its antigen-binding fragment may have a viral load (VL) with at least 98% sequence identity with SEQ ID NO: 25. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL with the amino acid sequence of SEQ ID NO: 25.

[00131] In some embodiments, humanized antibodies or antigen-binding fragments thereof that bind specifically to ILT7 comprising a VH are provided in this document, wherein the VH has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least Petition 870250083106, dated 09 / 15 / 2025, pp. 204 / 354 54 / 171 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 26. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 85% sequence identity with SEQ ID NO: 26. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 90% sequence identity with SEQ ID NO: 26. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 95% sequence identity with SEQ ID NO: 26. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 98% sequence identity with SEQ ID NO: 26. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VH with the amino acid sequence of SEQ ID NO: 26.

[00132] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising an HV are provided in this document, wherein the HV has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 27. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 85% sequence identity with SEQ ID NO: 27. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 90% sequence identity with SEQ ID NO: 27. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 95% sequence identity with SEQ ID NO: 27.The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 98% sequence identity with SEQ ID NO: 27. In some embodiments, humanized antibodies or... Petition 870250083106, dated 09 / 15 / 2025, pp. 205 / 354 55 / 171 antigen-binding fragments that bind specifically to ILT7, comprising a VH with the amino acid sequence SEQ ID NO: 27.

[00133] In some embodiments, humanized antibodies or antigen-binding fragments thereof that specifically bind to ILT7 comprising an HV are provided in this document, wherein the HV has at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 28. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 85% sequence identity with SEQ ID NO: 28. The humanized anti-ILT7 antibody or its antigen-binding fragment may have an HV with at least 90% sequence identity with SEQ ID NO: 28. The humanized anti-ILT7 antibody or its antigen-binding fragment may have a VH with at least 95% sequence identity with SEQ ID NO: 28.The humanized anti-ILT7 antibody or its antigen-binding fragment may have a viral load (VL) with at least 98% sequence identity with SEQ ID NO: 28. In some embodiments, humanized antibodies or antigen-binding fragments that specifically bind to ILT7 are provided in this document, comprising a VL with the amino acid sequence of SEQ ID NO: 28.

[00134] Anti-ILT7 antibodies or their antigen-binding fragments may comprise a combination of any VL disclosed in this document and any VH disclosed in this document. In some embodiments, VL and VH are connected by a linker. The linker may be flexible or rigid. In some embodiments, the linker has the amino acid sequence (GGGGS)n, n=1, 2, 3, 4 or 5 (SEQ ID NO: 35). In some embodiments, the linker has the amino acid sequence (EAAAK)n, n=1, 2, 3, 4 or 5 (SEQ ID NO: 36). In some embodiments, the linker has the amino acid sequence (PA)nP, n=1, 2, 3, 4 or 5 (SEQ ID NO: 37). Petition 870250083106, dated 09 / 15 / 2025, pp. 206 / 354 56 / 171

[00135] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments thereof comprising VL CDRs of a VL described in this document (SEQ ID NO: 9, 19, 20, 21 or 22) and / or VH CDRs of a VH described in this document (SEQ ID NO: 10, 23, 24, 25, 26, 27 or 28) are provided in this document. Methods for identifying CDRs are well known in the art. For example, software programs (abYsis) on publicly available websites are known to those knowledgeable in the field for antibody sequence analysis and CDR determination.

[00136] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document comprising (a) a VL comprising VL CDRs 1, 2 and 3 of a VL having the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH comprising VH CDRs 1, 2 and 3 of a VH having an amino acid sequence of SEQ ID NO: 10.

[00137] In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 are provided in this document, comprising (a) a VL comprising CDRs 1, 2 and 3 of a VL having an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22; and / or (b) a VH comprising CDRs of VH 1, 2 and 3 of a VH having an amino acid sequence selected from the group consisting of SEQ ID NOs: 23-28.

[00138] In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL comprises CDRs 1, 2 and 3 of a VL with the amino acid sequence of SEQ ID NO: 9. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL comprises CDRs 1, 2 and 3 of a VL with the amino acid sequence of SEQ ID NO: 19. In some Petition 870250083106, dated 09 / 15 / 2025, pp. 207 / 354 In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL comprises CDRs 1, 2 and 3 of a VL with the amino acid sequence of SEQ ID NO: 20. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL comprises CDRs 1, 2 and 3 of a VL with the amino acid sequence of SEQ ID NO: 21. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VL are provided in this document, wherein the VL comprises CDRs 1, 2 and 3 of a VL with the amino acid sequence of SEQ ID NO: 22.

[00139] In some embodiments, humanized antibodies or antigen-binding fragments thereof are provided in this document that specifically bind to ILT7 comprising a VH, wherein the VH comprises CDRs 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID NO: 10. In some embodiments, antibodies or antigen-binding fragments are provided in this document that specifically bind to ILT7 comprising a VH, wherein the VH comprises CDRs of VH 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID NO: 23. In some embodiments, antibodies or antigen-binding fragments are provided in this document that specifically bind to ILT7 comprising a VH, wherein the VH comprises CDRs of VH 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID NO: 24.In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VH are provided in this document, wherein the VH comprises CDRs of VH 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID NO: 25. In some embodiments, antibodies or antigen-binding fragments that specifically bind to ILT7 comprising a VH are provided in this document, wherein the VH comprises CDRs of VH 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID. Petition 870250083106, dated 09 / 15 / 2025, pp. 208 / 354 58 / 171 NO: 26. In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 comprising a VH are provided in this document, wherein the VH comprises CDRs of VH 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID NO: 27. In some embodiments, antibodies or antigen-binding fragments that bind specifically to ILT7 comprising a VH are provided in this document, wherein the VH comprises CDRs of VH 1, 2 and 3 of a VH with the amino acid sequence of SEQ ID NO: 28.

[00140] In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document is the antibody designated as cmAb12 (chimeric Ab12). In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document has a VL of cmAb12 (SEQ ID NO: 9). In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document has a VH of cmAb12 (SEQ ID NO: 10). The anti-ILT7 antibody or its antigen-binding fragment provided in this document may have both the VL and the VH of cmAb12. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document has a VL comprising VL CDRs 1, 2, and 3 of the VL of cmAb12 (SEQ ID NO: 9). In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document has an HV that comprises HV 1, 2, and 3 CDRs of cmAb12 HV (SEQ ID NO: 10).The anti-ILT7 antibody or its antigen-binding fragment provided in this document may have a VL comprising VL CDRs 1, 2, and 3 and a VH comprising VH CDRs 1, 2, and 3 of the VL and VH of cmAb12, respectively. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document is a variant of cmAb12. The cmAb12 variant may have a VL that is a variant of the cmAb12 VL having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions at SEQ ID NO: 9. The cmAb12 variant may have a VL that is... Petition 870250083106, dated 09 / 15 / 2025, pp. 209 / 354 59 / 171 a variant of the cmAb12 VL with up to about 5 amino acid substitutions, additions, and / or deletions in SEQ ID NO: 9. The cmAb12 variant may have a VH that is a variant of the cmAb12 VH having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in SEQ ID NO: 10. The cmAb12 variant may have a VH that is a variant of the cmAb12 VH with up to about 5 amino acid substitutions, additions, and / or deletions in SEQ ID NO: 10. Amino acid substitutions, additions, and / or deletions may be in VH CDRs or VL. In some embodiments, amino acid substitutions, additions, and / or deletions are not in CDRs. In some embodiments, the cmAb12 variant has up to about 5 conservative amino acid substitutions. In some embodiments, the cmAb12 variant has up to 3 conservative amino acid substitutions.In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document is a humanized antibody or antigen-binding fragment derived from cmAb12. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment provided in this document is a human antibody or antigen-binding fragment derived from cmAb12.

[00141] In some embodiments, humanized Ab12 antibodies (e.g., humanized Ab12, hu-cmAb12, hu-Ab12, or hu-12) are provided in this document. In some embodiments, the humanized anti-ILT7 antibody or its antigen-binding fragment provided in this document comprises a VL with an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22. In some embodiments, the humanized anti-ILT7 antibody or its antigen-binding fragment provided in this document comprises a VH with an amino acid sequence selected from SEQ ID NOs: 23-28. In some embodiments, the humanized anti-ILT7 antibody or its antigen-binding fragment provided in this document comprises a VL with an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22 and Petition 870250083106, dated 09 / 15 / 2025, pp. 210 / 354 60 / 171 a VH having an amino acid sequence selected from the group consisting of SEQ ID NOs: 23-28. In some embodiments, the anti-ILT7 antibody or its antigen-binding fragment provided in this document is a variant of a humanized Ab12 provided in this document. The variant may have a VL that is a variant of the VL of a humanized Ab12 having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22. The variant may have a VL that is a variant of the VL of a humanized Ab12 having up to about 5 amino acid substitutions, additions, and / or deletions in an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-22.The variant may have a VH that is a variant of the VH of a humanized Ab12 having up to about 3, about 5, about 8, about 10, about 12, or about 15 amino acid substitutions, additions, and / or deletions in a selected amino acid sequence from the group consisting of SEQ ID NOs: 23-28. The variant may have a VH that is a variant of the VH of a humanized Ab12 having up to about 5 amino acid substitutions, additions, and / or deletions in a selected amino acid sequence from the group consisting of SEQ ID NOs: 23-28. In some embodiments, the variant of a humanized Ab12 has up to about 5 conservative amino acid substitutions. In some embodiments, the humanized antibody is the “hu-cmAb12” antibody, that is, a humanized antibody comprising a VL with the amino acid sequence of SEQ ID NO: 19, and a VH with the amino acid sequence of SEQ ID NO: 26. Selected properties of the humanized hucmAB12 antibody are demonstrated in Examples 8-17.

[00142] In some embodiments, the anti-ILT7 antibodies provided in this document are IgA, IgD, IgE, IgG, or IgM antibodies. In some embodiments, the antibody is an IgA antibody. In some embodiments, the antibody is an IgD antibody. In some embodiments, the antibody is an IgE antibody. In some embodiments, the antibody is a Petition 870250083106, dated 09 / 15 / 2025, pp. 211 / 354 61 / 171 IgG antibody. In some embodiments, the antibody is an IgM antibody. In some embodiments, the antibodies provided in this document may be an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the antibody is an IgG1 antibody. In some embodiments, the antibody is an IgG2 antibody. In some embodiments, the antibody is an IgG3 antibody. In some embodiments, the antibody is an IgG4 antibody.

[00143] In some embodiments, the anti-ILT7 antibodies provided in this document comprise a light chain and a heavy chain. The light chain may comprise a constant light chain (CL) domain and a variable light chain (VL) domain. The heavy chain may comprise a variable heavy chain (VH) domain and a constant heavy chain (CH) domain. The VL / VH may be any VL / VH disclosed in this document. In some embodiments, the constant region of the light chain (CL) is kappa CL (Ck; SEQ ID NO: 29). In some embodiments, the constant region of the light chain (CL) is lambda CL ^λ; SEQ ID NO: 30). In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgA. In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgD. In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgE.In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgG. In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgM. In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgG1 (e.g., SEQ ID NO: 31). In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgG2 (e.g., SEQ ID NO: 32). In some embodiments, the heavy chain comprises a constant heavy chain (CH) domain of human IgG3 (e.g., SEQ ID NO: 33). In some embodiments, the heavy chain... Petition 870250083106, dated 09 / 15 / 2025, pp. 212 / 354 62 / 171 comprises a constant heavy chain (CH) domain of human IgG4 (e.g., SEQ ID NO: 34). All and any combinations of VL / VH pairs disclosed herein that specifically bind to ILT7 (e.g., human ILT7) and CL / CH pairs disclosed herein or otherwise known in the art are expressly contemplated herein.

[00144] Table 3B Constant region of the light chain Kappa sequences CL (Ck) RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY EKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 29) Lambda sequences CL (CA) GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVA WKADSSPVKAGVE IIIPSKQSNNKYAASSYLSLTPEQWK SHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 30)

[00145] Table 3C Constant region of the heavy chain IgG1 CH sequences ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPGK (SEQ ID NO: 31) IgG2 CH ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYV DGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKE YKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDISVEWESNGQPENNYKTTPPM LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPGK (SEQ ID NO: 32) IgG3 CH ASTKGPSVFPLAPCSRTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSSLSSVVTVPSSSLGTQT Petition 870250083106, dated 09 / 15 / 2025, pp. 213 / 354 63 / 171 YTCNVNHKPSNTKVDKRVELKTPLGDTTHTCPRCPEPKS CDTPPPCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPCPR CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH EDPEVQFKWYVDGVEVHNAKTKPREEQYNSTFRVVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKTKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESSGQP ENNYNTTPPMLDSDGSFFLYSKLTVDKSRWQQGNIFSCS VMHEALHNRFTQKSLSLSPGK (SEQ ID NO: 33) IgG4 CH ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKT YTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYV DGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYT QKSLSLSLGK (SEQ ID NO: 34)

[00146] In some embodiments, the antibodies provided in this document have a constant light chain (CL) region with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 29. In some embodiments, the antibodies provided in this document have a CL with the amino acid sequence of SEQ ID NO: 29. In some embodiments, the antibodies provided in this document have a constant light chain (CL) region with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 30. In some embodiments, the antibodies provided in this document have a CL with the amino acid sequence of SEQ ID NO: 30. In some embodiments, the antibodies provided in this document have a constant heavy chain (CH) region with at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity with SEQ ID NO: 31.In some embodiments, the antibodies provided in this document have a CH with the amino acid sequence SEQ ID NO: 31. In some embodiments, the antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least. Petition 870250083106, dated 09 / 15 / 2025, pp. 214 / 354 64 / 171 99% sequence identity with SEQ ID NO: 32. In some embodiments, the antibodies provided in this document have a CH with the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 33. In some embodiments, the antibodies provided in this document have a CH with the amino acid sequence of SEQ ID NO: 33. In some embodiments, the antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 34. In some embodiments, the antibodies provided in this document have a CH with the amino acid sequence of SEQ ID NO: 34.

[00147] In some embodiments, antibodies or antigen-binding fragments that compete with the antibody or antigen-binding fragment provided above for binding to ILT7 (e.g., human ILT7) are also provided in this document. Antibodies that “compete with another antibody for binding to a target” refer to antibodies that inhibit (partially or completely) the binding of the other antibody to the target. The competition between two antibodies for binding to a target, i.e., whether and to what extent one antibody inhibits the binding of the other antibody to a target, can be determined using known competition experiments, for example, BIACORE® surface plasmon resonance (SPR) analysis. In some embodiments, an anti-ILT7 antibody or antigen-binding fragment competes with, and inhibits, the binding of another antibody or antigen-binding fragment to ILT7 by at least 50%, 60%, 70%, 80%, 90%, or 100%.Competition assays can be conducted as described, for example, in Ed Harlow and David Lane, Cold Spring Harbor Protocol; 2006; doi: l0.H0l / pdb.prot4277 or in Chapter 11 of “Using Antibodies” by Ed Harlow and David Lane, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA 1999. Petition 870250083106, dated 09 / 15 / 2025, pp. 215 / 354 65 / 171

[00148] In some embodiments, antibodies or antigen-binding fragments are provided in this document that compete with an anti-ILT7 antibody or antigen-binding fragment disclosed in this document for binding to ILT7 (e.g., human ILT7). In some embodiments, antibodies or antigen-binding fragments are provided in this document that compete with chimeric Ab12 for binding to ILT7 (e.g., human ILT7). In some embodiments, antibodies or antigen-binding fragments are provided in this document that compete with a humanized Ab12 disclosed in this document for binding to ILT7 (e.g., human ILT7).

[00149] Epitope mapping is a method of identifying the binding site, region, or epitope on a target protein where an antibody binds. A variety of methods are known in the art for mapping epitopes on target proteins. These methods include mutagenesis, including but not limited to shotgun mutagenesis, site-directed mutagenesis, and alanine scanning; domain or fragment scanning; peptide scanning (e.g., Pepscan technology); display methods (e.g., phage display, microbial display, and ribosome / mRNA display); methods involving proteolysis and mass spectrometry; and structural determination (e.g., X-ray crystallography and NMR).In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are characterized by assays including, but not limited to, N-terminal sequencing, amino acid analysis, HPLC, mass spectrometry, ion-exchange chromatography, and papain digestion.

[00150] As provided in more detail in the Experimental section below, Ab12 does not compete for binding to human ILT7 with the reference antibody daxdilimab. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments provided in this document do not compete for binding to human ILT7 with daxdilimab. Petition 870250083106, dated 09 / 15 / 2025, pp. 216 / 354 66 / 171

[00151] The anti-ILT7 antibodies or antigen-binding fragments of this disclosure can be analyzed for their physical, chemical, and / or biological properties by various methods known in the art. In some embodiments, an anti-ILT7 antibody is tested for its ability to bind to ILT7 (e.g., human ILT7). In some embodiments, an anti-ILT7 antibody is tested for its ability to bind to an FcyR. In some embodiments, an anti-ILT7 antibody is tested for its ability to bind to FcyRIIA / CD32A. In some embodiments, an anti-ILT7 antibody is tested for its ability to bind to FcyRIIIA / CD16A. Binding assays include, but are not limited to, BLI, SPR (e.g., Biacore), ELISA, and FACS. In addition, antibodies can be evaluated for solubility, stability, thermostability, viscosity, expression levels, expression quality, and / or purification efficiency.

[00152] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with high affinity, for example, with a Kd of 10⁻⁶M or less, 5χ¹⁰⁷M or less, 10⁻⁷M or less, 5χ¹⁰⁸M or less, 10⁻⁸M or less, 5χ¹⁰⁹M or less, 10⁻⁹M or less, 5χ¹⁰⁻¹⁰M or less, or 10⁻¹⁰M or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with a Kd of 5χ¹⁰⁷M or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with high affinity, for example, with a Kd of about 10-6M, about 5χ10-7M, about 10-7M, about 5χ10-8M, about 10-8M, about 5χ109M, about 10-9M, about 5χ10-10M or about 10-10M.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with a Kd of approximately 107M. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with a Kd. Petition 870250083106, dated 09 / 15 / 2025, pp. 217 / 354 67 / 171 ranging from 10⁻¹⁰M to 10⁻⁶M, from 10⁻⁹M to 10⁻⁶M, from 10⁻⁸M to 10⁻⁶M, from 10⁻⁷M to 10⁻⁶M, from 10⁻¹⁰M to 5x10⁻⁷M, from 10⁻⁹M to 5x10⁻⁷M, from 10⁻⁸M to 5x10⁻⁷M, or from 10⁻⁷M to 5x10⁻⁷M. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with high affinity, for example, with a Kd of 10⁻⁷M to 10⁻⁶M. In some embodiments, the Kd is determined by BLI. In some embodiments, the Kd is determined by SPR. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to human ILT7 with high affinity, for example, with a Kd of 10⁻⁶M or less, 5x10⁻⁷M or less, 10⁻⁷M or less, 5x10⁻⁸M or less, 10⁻⁸M or less, 5x10⁻⁹M or less, 10⁻⁹M or less, 5x10⁻¹⁰M or less, or 10⁻¹⁰M or less; of 10-7M to 5x10-7M as measured by SPR.。

[00153] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document bind to both human ILT7 and cynomolgus ILT7.

[00154] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document do not bind to other members of the LILR family. In some embodiments, the affinities of the anti-ILT7 antibodies or antigen-binding fragments described in this document for other proteins belonging to the LILR family are comparable to those of an isotype antibody (e.g., hIgG1). Other proteins in the LILR family include, but are not limited to: LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3, and LILB5. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document do not bind to one or more proteins belonging to the LILR family selected from the group consisting of LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3, and LILB5. In some Petition 870250083106, dated 09 / 15 / 2025, pp. 218 / 354 68 / 171 embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document does not bind to any of the proteins belonging to the LILR family: LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3, and LILB5.

[00155] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of IFNα by PBMCs. In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of α by CpG-stimulated PBMCs in vitro. In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of α by PBMCs in vivo. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document reduce the level of α in vivo. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 of 10 nM or less, 5 nM or less, 1 nM or less, 0.5 nM or less, 0.1 nM or less, 0.08 nM or less, 0.05 nM or less, or 0.01 nM or less.In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 of 0.1 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 of approximately 10 nM, approximately 5 nM, approximately 1 nM, approximately 0.5 nM, approximately 0.1 nM, approximately 0.08 nM, approximately 0.05 nM, or approximately 0.01 nM. In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 of approximately 0.05 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 ranging from... Petition 870250083106, dated 09 / 15 / 2025, pp. 219 / 354 69 / 171 0.01 nM to 10 nM, 0.01 nM to 5 nM, 0.01 nM to 1 nM, 0.01 nM to 0.5 nM, 0.01 nM to 0.1 nM, or 0.01 nM to 0.05 nM. In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit IFNα release by CpG-stimulated PBMCs in vitro with an EC50 of 0.01 nM to 0.1 nM. In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit IFNα release by CpG-stimulated PBMCs in vitro with an EC50 of 0.01 nM to 1 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 that is 60% or less, 50% or less, 40% or less, or 30% or less of that of the reference antibody daxdilimab.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 that is 50% or less of that of the reference antibody daxdilimab. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 that is 10-60%, 10-50%, 10-40%, 20-60%, 20-50%, or 20-40% of that of the reference antibody daxdilimab. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document inhibit the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 that is 10-50% of that of the reference antibody daxdilimab.

[00156] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document selectively bind to pDCs in human PBMCs. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document do not bind to T cells, B cells, NK cells, NKT cells, or monocytes in PBMCs.

[00157] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit activities Petition 870250083106, dated 09 / 15 / 2025, pp. 220 / 354 70 / 171 ADCC and ADCP activities against cells expressing ILT7, such as pDCs. ADCC activity can be NK-dependent. ADCC activity can be neutrophil-dependent. In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document deplete pDCs in vivo.

[00158] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.008 nM or less, 0.005 nM or less, 0.002 nM or less, or 0.001 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of 0.01 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of 0.008 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of 0.005 nM or less.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of approximately 0.05 nM, approximately 0.02 nM, approximately 0.01 nM, approximately 0.008 nM, approximately 0.005 nM, approximately 0.002 nM, or approximately 0.001 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of approximately 0.008 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 of approximately 0.005 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 ranging from 0.001 nM to 0.05 nM, from 0.001 nM to 0.02 nM. Petition 870250083106, dated 09 / 15 / 2025, pp. 221 / 354 71 / 171 from 0.001 nM to 0.01 nM, from 0.001 nM to 0.05 nM, from 0.005 nM to 0.05 nM, from 0.005 nM to 0.02 nM, from 0.005 nM to 0.01 nM, or from 0.001 nM to 0.05 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 ranging from 0.001 nM to 0.01 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 that is 10-60%, 10-50%, 10-40%, 20-60%, 20-50%, or 20-40% of that of the reference antibody daxdilimab. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 that is 10-50% of that of the reference antibody daxdilimab.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit NK-dependent ADCC activity with an EC50 that is approximately 40% of that of the reference antibody daxdilimab.

[00159] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with an EC50 of 500 nM or less, 200 nM or less, 100 nM or less, 80 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 5 nM or less, or 1 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with an EC50 of 100 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with an EC50 of 50 nM or less.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with a... Petition 870250083106, dated 09 / 15 / 2025, pp. 222 / 354 72 / 171 EC50 ranging from 1 nM to 500 nM, from 1 nM to 200 nM, from 1 nM to 100 nM, from 1 nM to 80 nM, from 1 nM to 50 nM, from 1 nM to 20 nM, from 5 nM to 500 nM, from 5 nM to 200 nM, from 5 nM to 100 nM, from 5 nM to 80 nM, from 5 nM to 50 nM, or from 5 nM to 20 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with an EC50 ranging from 1 nM to 50 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with an EC50 of approximately 500 nM, approximately 200 nM, approximately 100 nM, approximately 80 nM, approximately 50 nM, approximately 20 nM, approximately 10 nM, approximately 5 nM, or approximately 1 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit neutrophil-dependent ADCC activity with an EC50 of approximately 10 nM.

[00160] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 of 10 nM or less, 8 nM or less, 5 nM or less, 2 nM or less, 1 nM or less, 0.5 nM or less, 0.2 nM or less, or 0.1 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 of 10 nM or less. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 of 8 nM or less.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 of approximately 10 nM, approximately 8 nM, approximately 5 nM, approximately 2 nM, approximately 1 nM, approximately 0.5 nM, approximately 0.2 nM, or approximately 0.1 nM. In some embodiments, the antibodies... Petition 870250083106, dated 09 / 15 / 2025, pp. 223 / 354 The anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 of approximately 1 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 ranging from 0.01 to 100 nM, 0.01 to 50 nM, 0.01 to 10 nM, 0.1 to 100 nM, 0.1 to 50 nM, 0.1 to 10 nM, or 0.1 to 5 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 ranging from 0.1 to 10 nM. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit macrophage-dependent ADCP activity with an EC50 ranging from 0.5 to 5 nM.

[00161] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit a maximum phagocytic index of at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, or at least 80%. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit a maximum phagocytic index of approximately 20%, approximately 30%, approximately 40%, approximately 50%, approximately 60%, approximately 70%, or approximately 80%. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit a maximum phagocytic index ranging from 20 to 80%, 20 to 70%, 20 to 60%, 30 to 80%, 30 to 70%, or 30 to 60%. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit a maximum phagocytic index ranging from 20 to 80%.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document exhibit a maximum phagocytic index ranging from 30 to 60%. Petition 870250083106, dated 09 / 15 / 2025, pp. 224 / 354 74 / 171 C. VARIANTS AND CONJUGATES

[00162] This disclosure also includes additional variants and equivalents that are substantially homologous to the recombinant, monoclonal, chimeric, humanized, and human antibodies, or antibody fragments thereof, described in this document. In some embodiments, it is desirable to improve the antibody binding affinity. In some embodiments, it is desirable to modulate the antibody's biological properties, including, but not limited to, specificity, thermostability, expression level, effector function(s), glycosylation, immunogenicity, and / or solubility. Experts in the field will recognize that amino acid changes can alter post-translational processes of an antibody, such as altering the number or position of glycosylation sites or altering membrane anchoring characteristics.

[00163] Variations can be a substitution, deletion, or insertion of one or more nucleotides that encode the antibody or polypeptide, resulting in an alteration in the amino acid sequence compared to the native sequence of the antibody or polypeptide. In some embodiments, amino acid substitutions result from the replacement of one amino acid with another amino acid with similar structural and / or chemical properties, such as the substitution of leucine for serine, for example, conservative amino acid substitutions. Insertions or deletions can be in the range of about 1 to 5 amino acids.In some embodiments, the substitution, deletion, or insertion involves fewer than 25 amino acid substitutions, fewer than 20 amino acid substitutions, fewer than 15 amino acid substitutions, fewer than 10 amino acid substitutions, fewer than 5 amino acid substitutions, fewer than 4 amino acid substitutions, fewer than 3 amino acid substitutions, or fewer amino acid substitutions relative to the original molecule. In some embodiments, variations in the amino acid sequence that are biologically useful and / or relevant can be determined by systematically making insertions, deletions, or... Petition 870250083106, dated 09 / 15 / 2025, pp. 225 / 354 75 / 171 substitutions in the sequence and testing the activity of the resulting variant proteins in comparison with the original protein.

[00164] In some embodiments, variants of anti-ILT7 antibodies or antigen-binding fragments described in this document are provided in this document. In some embodiments, variants of the anti-ILT7 Ab12 antibody clone (cmAb12 or hu-Ab12) are provided in this document. In some embodiments, a variant comprises from one to 30 amino acid substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment. In some embodiments, a variant comprises from one to 25 amino acid substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment. In some embodiments, a variant comprises from one to 20 substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment. In some embodiments, a variant comprises from one to 15 substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment.In some embodiments, a variant comprises from one to 10 substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment. In some embodiments, a variant comprises from one to five amino acid substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment. In some embodiments, a variant comprises from one to three amino acid substitutions, additions, and / or deletions in the original antibody or antigen-binding fragment. In some embodiments, the amino acid substitution(s) is / are located in a CDR of the antibody or antigen-binding fragment. In some embodiments, the amino acid substitution(s) is / are not located in a CDR of the antibody or antigen-binding fragment. In some embodiments, the amino acid substitution(s) is / are located in a structural region of the antibody or antigen-binding fragment.In some modalities, substitutions, additions, and / or deletions of amino acids are conservative amino acid substitutions. Petition 870250083106, dated 09 / 15 / 2025, pp. 226 / 354 76 / 171

[00165] It is known in the art that the constant region(s) of an antibody mediate various effector functions, and these effector functions can vary depending on the antibody isotype. For example, the binding of the C1 component of complement to the Fc region of IgG or IgM antibodies (bound to the antigen) activates the complement system. Complement activation is important in the opsonization and lysis of cellular pathogens. Complement activation also stimulates the inflammatory response and may be involved in autoimmune hypersensitivity. In addition, the Fc region of an antibody can bind to a cell that expresses an Fc receptor (FcR). There are several Fc receptors that are specific for different classes of antibodies, including IgG (gamma receptors), IgE (epsilon receptors), IgA (alpha receptors), and IgM (mu receptors).The binding of antibodies to Fc receptors on cell surfaces triggers a series of important and diverse biological responses, including the engulfment and destruction of antibody-coated particles, the elimination of immune complexes, the lysis of antibody-coated target cells by killer cells (called antibody-dependent cellular cytotoxicity or ADCC), the release of inflammatory mediators, placental transfer, and the control of immunoglobulin production.

[00166] As is known in the art, allotypes are polymorphic markers of an IG subclass that correspond to amino acid changes and are serologically detected by antibody reagents. Among others, the allotypes of the human gamma heavy chains of IgG are designated as Gm (“gamma marker”). The G1m, G2m, and G3m allotypes are carried by the constant region of the gamma1, gamma2, and gamma3 chains, encoded by the IGHG1, IGHG2, and IGHG3 genes, respectively. The gamma1 chains can express G1m alleles (combinations of G1m allotypes): G1m3; G1m3,1; G1m17,1; G1m17,1,2; G1m17,1,27; Gm17,1,28; and Gm17,1,27,28. The C regions of the G1m3,1 chains; G1m17,1; and G1m17,1,2 differ from the G1m3 chains by two, three, and four amino acids, respectively. The correspondence between the G1m and IGHG1 alleles is known in the art, for example, Lefranc, Petition 870250083106, dated 09 / 15 / 2025, pp. 227 / 354 77 / 171 Chapter 26 - Analysis of the IMGT® immunoglobulin repertoire and antibody humanization, Molecular Biology of B Cells (second edition), Academic Press, 2015, pages 481-514 (Table 7). In IGHG1 CH1, lysine at position 120 (K120) on the G strand corresponds to the G1m17 allotype. Isoleucine I103 (F strand) is specific to the gamma chain isotype. If an arginine is expressed at position 120 (R120), the simultaneous presence of R120 and I103 corresponds to the expression of the G1m3 allotype. For the gamma3 and gamma4 isotypes (which also have R120, but T at 103), R120 corresponds only to the expression of the nG1m17 isoallotype (an isoallotype or nGm is detected by antibody reagents that identify this marker as an allotype in one IgG subclass and as an isotype for other subclasses). In IGHG1 CH3, aspartate D12 and leucine L14 (A-strand) correspond to G1m1, while glutamate E12 and methionine M14 correspond to the nG1m1 isoallotype.A glycine at position 110 corresponds to G1m2, while an alanine does not correspond to any allotype (negative chain for G1m2).

[00167] See exemplary allotypes of the constant region of the human IgG1 heavy chain (IgG1 CH) below. In some embodiments, IgG1 antibodies having a constant region of the heavy chain (CH) having at least 85% sequence identity with a selected amino acid sequence from the group consisting of SEQ ID NOs: 31 and 40-44 are provided in this document. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 31. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 40. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 41.In some modalities, the IgG1 antibodies provided in this... Petition 870250083106, dated 09 / 15 / 2025, pp. 228 / 354 78 / 171 document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 42. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 43. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 44.

[00168] 3D Table Alótipo Sequências IgG1 alotipo 0 - CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 31) IgG1 alotipo 1 - CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 40) IgG1 alotipo 2 - CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG K (SEQ ID NO: 41) Petition 870250083106, of 15 / 09 / 2025, p. 229 / 354 79 / 171 IgG1 alotipo 3 - CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNIFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 42) IgG1 alotipo 4 - CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNRYTQKSLSLSPGK (SEQ ID NO: 43) IgG1 alotipo 5 - CH ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEGLHNHTTQKSLSLSPGK (SEQ ID NO: 44) [001 69] The gamma2 chains can express G2m alleles. The position 45.1 (first position of the CD transverse strand) corresponds to the presence of the single identified G2m allotype (G2m23) or its absence (G2m..). Valine V45.1 corresponds to G2m.., while a methionine would correspond to G2m23.

[00170] The gamma3 chains can express G3m alleles (combinations of G3m allotypes). G3m16 (W83) and G3m21 (L82), nG3m21 (P82) are located on CH2. The other G3m allotypes form two mosaics on CH3. G3m26 (R115), G3m5 (R115, F116), G3m28 (R115, Y116), nG3m5 (H115, Y116), G3m14 (M84, R115, F116) and G3m15 (M39, H115, Y116) form a first mosaic. G3m11 (S44), nG3m11 (N44), G3m10 (S44, I101), G3m24 Petition 870250083106, dated 09 / 15 / 2025, pp. 230 / 354 80 / 171 (S44, V101), G3m27 (I101), G3m6 (S44, E98), G3m13 (S44, Q98) form a second mosaic.

[00171] In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgA antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgD antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgE antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgM antibody.In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG1 antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG2 antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG3 antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG4 antibody. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG1 antibody, wherein the IgG1 antibody may be of any allotype known in the art.In some forms, the IgG1 antibody is of the allotype G1m3; G1m3,1; G1m17,1; G1m17,1,2; G1m17,1,27;. Gm17,1,28; or Gm17,1,27,28. In some modalities, the IgG1 antibody is of the G1m3 allotype. In some modalities, the IgG1 antibody is of the G1m3,1 allotype. Petition 870250083106, dated 09 / 15 / 2025, pp. 231 / 354 81 / 171 In some embodiments, the IgG1 antibody is of the G1m17,1 allotype. In some embodiments, the IgG1 antibody is of the G1m17,1,2 allotype. In some embodiments, the IgG1 antibody is of the Gm17,1,28 allotype. In some embodiments, the IgG1 antibody is of the Gm17,1,27,28 allotype. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG2 antibody, wherein the IgG2 antibody may be of any allotype known in the art. In some embodiments, the IgG2 antibody is of the G2m23 allotype. In some embodiments, the IgG2 antibody is of the G2m allotype. In some embodiments, the anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of a human IgG3 antibody, wherein the IgG3 antibody may be of any allotype known in the art.In some embodiments, the IgG3 antibody is of allotype G3m16, G3m21, G3m26, G3m5, G3m28, G3m14, G3m15, G3m11, G3m10, G3m24, G3m27, G3m6, or G3m13. In some embodiments, the IgG3 antibody is of allotype G3m16. In some embodiments, the IgG3 antibody is of allotype G3m21. In some embodiments, the IgG3 antibody is of allotype G3m26. In some embodiments, the IgG3 antibody is of allotype G3m5. In some embodiments, the IgG3 antibody is of allotype G3m28. In some embodiments, the IgG3 antibody is of allotype G3m14. In some embodiments, the IgG3 antibody is of allotype G3m15. In some modalities, the IgG3 antibody is of allotype G3m11. In some modalities, the IgG3 antibody is of allotype G3m10. In some modalities, the IgG3 antibody is of allotype G3m24. In some modalities, the IgG3 antibody is of allotype G3m27. In some modalities, the IgG3 antibody is of allotype G3m6. In some modalities, the IgG3 antibody is of allotype G3m13.

[00172] In some embodiments, at least one or more constant regions have been modified or deleted in the anti-ILT7 antibody or antigen-binding fragment described in this document. In some embodiments, the antibodies comprise modifications in one or more of the Petition 870250083106, dated 09 / 15 / 2025, pp. 232 / 354 82 / 171 three constant regions of the heavy chain (CH1, CH2 or CH3) and / or in the constant region of the light chain (CL).

[00173] In some embodiments, the constant region of the modified antibody heavy chain comprises at least one human constant region. In some embodiments, the constant region of the modified antibody heavy chain comprises more than one human constant region. In some embodiments, modifications to the constant region comprise additions, deletions, or substitutions of one or more amino acids in one or more regions. In some embodiments, one or more regions are partially or totally deleted from the constant regions of the modified antibodies. In some embodiments, the entire CH2 domain has been removed from an antibody (Δ^2 constructs). In some embodiments, a deleted constant region is replaced by a short amino acid spacer that provides some of the molecular flexibility normally conferred by the missing constant region. In some embodiments, a modified antibody comprises a CH3 domain directly fused to the antibody hinge region.In some embodiments, a modified antibody comprises a peptide spacer inserted between the hinge region and the modified CH2 and / or CH3 domains.

[00174] In some embodiments, an anti-ILT7 antibody or antigen-binding fragment comprises an Fc region. In some embodiments, the Fc region is fused via a hinge. The hinge may be an IgG1 hinge, an IgG2 hinge, or an IgG3 hinge. The amino acid sequences of the Fc region of human IgG1, IgG2, IgG3, and IgG4 are known to those with common knowledge in the field. In some cases, Fc regions with amino acid variations have been identified in native antibodies. In some embodiments, modified antibodies (e.g., modified Fc region) provide altered effector functions that, in turn, affect the antibody's biological profile. For example, in some embodiments, the deletion or inactivation (via point mutations or other means) of a constant region reduces the antibody's Fc receptor binding. Petition 870250083106, dated 09 / 15 / 2025, pp. 233 / 354 83 / 171 modified as it circulates. In some embodiments, modifications to the constant region reduce the immunogenicity of the antibody. In some embodiments, modifications to the constant region increase the serum half-life of the antibody. In some embodiments, modifications to the constant region reduce the serum half-life of the antibody. In some embodiments, modifications to the constant region increase the ADCC and / or complement-dependent cytotoxicity (CDC) of the antibody. In some embodiments, modifications to the constant region increase the antibody-dependent cellular phagocytosis (ADCP) of the antibody. In some embodiments, modifications to the constant region decrease or remove ADCC and / or CDC from the antibody. In some embodiments, specific amino acid substitutions in an Fc region of human IgG1 with corresponding IgG2 or IgG4 residues reduce effector functions (e.g., ADCC and CDC) in the modified antibody.In some embodiments, an antibody lacks one or more effector functions (e.g., “effector-less” antibodies). In some embodiments, the antibody does not bind to an Fc receptor and / or complement factors. In some embodiments, the antibody has no effector function(s). In some embodiments, modifications to the constant region increase or enhance the antibody's ADCC and / or ADCP. In some embodiments, the constant region is modified to eliminate disulfide bonds or oligosaccharide fragments. In some embodiments, the constant region is modified to add / substitute one or more amino acids to provide one or more cytotoxin, oligosaccharide, or carbohydrate binding sites. In some embodiments, an anti-ILT7 antibody or antigen-binding fragment comprises a variant Fc region that is engineered with substitutions at specific amino acid positions compared to a native Fc region.

[00175] In some embodiments, an anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of the IgG1 heavy chain comprising one or more amino acid substitutions selected from the group consisting of L234, Petition 870250083106, dated 09 / 15 / 2025, pp. 234 / 354 84 / 171 L235, G236, S239, F243, H268, D270, R292, S298, Y300, V305, A330, I332, K326, E333, K334 and P396, numbered according to the EU Index.

[00176] In some embodiments, an anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of the IgG1 heavy chain comprising at least one amino acid substitution. The constant region of the IgG1 heavy chain may comprise an L234 substitution. The L234 substitution may be, for example, L234Y. The constant region of the IgG1 heavy chain may comprise an L235 substitution. The L235 substitution may be, for example, L235Q or L235V. The constant region of the IgG1 heavy chain may comprise a G236 substitution. The G236 substitution may be, for example, G236A or G236W. The constant region of the IgG1 heavy chain may comprise an S239 substitution. The S239 substitution may be, for example, S239D or S239M. The constant region of the IgG1 heavy chain may comprise an F243 substitution. The replacement F243 could be, for example, F243L.The constant region of the IgG1 heavy chain may comprise an H268 substitution. The H268 substitution may be, for example, H268D. The constant region of the IgG1 heavy chain may comprise a D270 substitution. The D270 substitution may be, for example, D270E. The constant region of the IgG1 heavy chain may comprise an R292 substitution. The R292 substitution may be, for example, R292P. The constant region of the IgG1 heavy chain may comprise an S298 substitution. The S298 substitution may be, for example, S298A. The constant region of the IgG1 heavy chain may comprise a Y300 substitution. The Y300 substitution may be, for example, Y300L. The constant region of the IgG1 heavy chain may comprise a V305 substitution. The V305 substitution may be, for example, V305I. The constant region of the IgG1 heavy chain may comprise a K326 substitution. The replacement K326 could be, for example, K326D.The constant region of the IgG1 heavy chain may comprise an A330 substitution. The A330 substitution may be, for example... Petition 870250083106, dated 09 / 15 / 2025, pages 235 / 354 85 / 171 example, A330M or A330L. The constant region of the IgG1 heavy chain may comprise an I332 substitution. The I332 substitution may be, for example, I332E. The constant region of the IgG1 heavy chain may comprise an E333 substitution. The E333 substitution may be, for example, E333A. The constant region of the IgG1 heavy chain may comprise a K334 substitution. The K334 substitution may be, for example, K334A or K334E. The constant region of the IgG1 heavy chain may comprise a P396 substitution. The P396 substitution may be, for example, P396L.

[00177] In some embodiments, an anti-ILT7 antibody or antigen-binding fragment described in this document comprises a constant region of the IgG1 heavy chain comprising one or more amino acid substitutions selected from the group consisting of L234Y, L235Q, L235V, G236A, G236W, S239D, S239M, F243L, H268D, D270E, R292P, S298A, Y300L, V305I, K326D, A330M, A330L, I332E, E333A, K334A, K334E and P396L, numbered according to the EU Index. In some embodiments, the constant region of the IgG1 heavy chain comprises one or more amino acid substitutions selected from the group consisting of K214R, L234A, L235E, G237A, A330S, P331S, D356E, and L358M, numbered according to the EU Index. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described herein comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions S298A, E333A, and K334A.In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions S239D and I332E. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions S239D, A330L, and I332E. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments... Petition 870250083106, dated 09 / 15 / 2025, pp. 236 / 354 The 86 / 171 described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitution G236A. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions G236A, S239D, and I332E. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions G236A, A330L, and I332E. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions G236A, S239D, A330L, and I332E.In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions F243L, R292P, Y300L, V305I, and P396L. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions L235V, F243L, R292P, Y300L, and P396L. In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by the amino acid substitutions L234Y, L235Q, G236W, S239M, H268D, D270E, and S298A.In some embodiments, the anti-ILT7 antibodies and antigen-binding fragments described in this document comprise a variant of the constant region of the human IgG1 heavy chain modified by amino acid substitutions D270E, K326D, A330M, and K334E. All are numbered according to the EU Index. Below are provided the constant regions of the heavy chain (HC) of exemplary IgG1 allotypes with different [unclear / phrased] Petition 870250083106, dated 09 / 15 / 2025, pp. 237 / 354 87 / 171 mutations that increase or enhance antibody ADCC and / or ADCP. Expressly contemplated for inclusion in antibodies disclosed in this document is the constant region of the heavy chain (CH) of any immunoglobulin (e.g., human IgG1) disclosed in this document or otherwise known in the art with any combinations of mutations disclosed in this document or otherwise known in the art to increase or enhance antibody ADCC and / or ADCP.

[00178] Table 3E Constant region of the heavy chain of IgG1 IgG1 sequences allotype 0-AAA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNATYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIAATISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK (SEQ ID NO: 45) IgG1 allotype 0-DE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP DVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPEEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK (SEQ ID NO: 46) IgG1 allotype 0-DLE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP DVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS Petition 870250083106, dated 09 / 15 / 2025, pp. 238 / 354 88 / 171 DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK (SEQ ID NO: 47) IgG1 alotipo 0-G236A ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK (SEQ ID NO: 48) IgG1 alotipo 0-LPLIL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLLPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPPEEQYNSTLRVVSILTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPLVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK (SEQ ID NO: 49) IgG1 alotipo 1-AAA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNATYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIATISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK (SEQ ID NO: 50) IgG1 allotype 1-DLE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG PDVFLPPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPLPEEKTISKAGQPREPQVYTLPPSRDELT KNQVS LTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK (SEQ ID NO: 51) Petition 870250083106, de 15 / 09 / 2025, pág. 239 / 354 89 / 171 IgG1 alotipo 1-ALE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK (SEQ ID NO: 52) IgG1 alotipo 2-AAA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNATYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIAATISKAKGQPREPQVYTLPPSREEMT KNQVS LTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGK (SEQ ID NO: 53) IgG1 alotipo 2-G236A ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAGGQPREPQVYTLPPSREEMTK NQVSLTCLVKGGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK (SEQ ID NO: 54) IgG1 alotipo 2-ADE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLAGP DVFLFPKPKDTLMISRTPEVTVCVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPEEKTISKAGGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGK (SEQ ID NO: 55) IgG1 alotipo 3-AAA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICVNNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV Petition 870250083106, de 15 / 09 / 2025, pág. 240 / 354 90 / 171 DGVEVHNAKTKPREEQYNATYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIAATISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNHYTQKSL SLSPGK (SEQ ID NO: 56) IgG1 alotipo 3-ADLE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLAGP DVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNHYTQKS LSLSPGK (SEQ ID NO: 57) IgG1 alotipo 3-LPLIL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLLPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPPEEQYNSTLRVVSILTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPLVLDSD GSFFLYSKLTVDKSRWQQGNIFSCSVMHEALHNHYTQKSL SLSPGK (SEQ ID NO: 58) IgG1 alotipo 4-AAA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICVNNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNATYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIATISKAGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRYTQKSL SLSPGK (SEQ ID NO: 59) IgG1 alotipo 4-DLE ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICVNNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP DVFLFPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPLPEEKTISKAGQPREPQVYTLPPSRDELTK NQVSLTCLVKGGFYPSDIAVEWESNGQPENNYKTTPPVLDS Petition 870250083106, de 15 / 09 / 2025, pág. 241 / 354 91 / 171 DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRYTQK SLSLSPGK (SEQ ID NO: 60) IgG1 alotipo 4-LPLIL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLLPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPPEEQYNSTLRVVSILTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPLVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNRYTQKSL SLSPGK (SEQ ID NO: 61) IgG1 alotipo 5-AAA ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNATYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIAATISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEGLHNHTTQKSL SLSPGK (SEQ ID NO: 62) IgG1 alotipo 5-LPLIL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT YICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLLPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPPEEQYNSTLRVVSILTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPLVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEGLHNHTTQKSL SLSPGK (SEQ ID NO: 63) IgG1 allotype 5-VLPLL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPPAVLQSSGLYSLSSVVTVPSSSLGTQT YICVNNHKPSNTKVDKKVEKPKSCDKTHTCPPCPEPALVGG PSVFLLPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPPEEQYNSTLRVVSVLTVLHQDWLNGKE YCKKVSNKALPAPIEKTISKAGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPLVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEGLHNHTTQK SLSLSPGK (SEQ ID NO: 64) Petition 870250083106, de 15 / 09 / 2025, pág. 242 / 354 92 / 171

[00179] In some embodiments, IgG1 antibodies having a constant heavy chain (CH) region having at least 85% sequence identity with a selected amino acid sequence from the group consisting of SEQ ID NOs: 45-64 are provided in this document. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 45. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 46. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 47.In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 48. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 49. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 50. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity. sequence with SEQ ID NO: 51.In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 52. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%. Petition 870250083106, dated 09 / 15 / 2025, pp. 243 / 354 93 / 171 or at least 99% sequence identity with SEQ ID NO: 53. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 54. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 55. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 56. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 57.In some embodiments, the IgG1 antibodies provided in this document have a sequence identity (CH) with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% with SEQ ID NO: 58. In some embodiments, the IgG1 antibodies provided in this document have a sequence identity (CH) with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% with SEQ ID NO: 59. In some embodiments, the IgG1 antibodies provided in this document have a sequence identity (CH) with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% with SEQ ID NO: 60. In some embodiments, the IgG1 antibodies provided in this document have a sequence identity (CH) with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% with SEQ ID NO: 60. sequence with SEQ ID NO: 61.In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 62. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%. Petition 870250083106, dated 09 / 15 / 2025, pp. 244 / 354 94 / 171 or at least 99% sequence identity with SEQ ID NO: 63. In some embodiments, the IgG1 antibodies provided in this document have a CH with at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 64.

[00180] In some embodiments, the supplied antibody or antigen-binding fragment includes a CH with the amino acid sequence SEQ ID NO: 55. In some embodiments (e.g., embodiments in which the antibody or antigen-binding fragment is the humanized antibody hu-cmAb12), the antibody or antigen-binding fragment includes a CH with the amino acid sequence SEQ ID NO: 55, a VH with the amino acid sequence SEQ ID NO: 26, and a VL with the amino acid sequence SEQ ID NO: 19. In some embodiments, the antibody or antigen-binding fragment includes a CH with the amino acid sequence SEQ ID NO: 55, a CL with the amino acid sequence SEQ ID NO: 30, a VH with the amino acid sequence SEQ ID NO: 26, and a VL with the amino acid sequence SEQ ID NO: 19. Selected properties of the humanized antibody hu-cmAB12 are demonstrated in the Examples. 8-17.

[00181] In some embodiments, variants may include the addition of amino acid residues at the amino and / or carboxyl terminus of the antibody or polypeptide. The length of additional amino acid residues may vary from one residue to one hundred or more residues. In some embodiments, a variant comprises an N-terminal methionyl residue. In some embodiments, the variant comprises an additional polypeptide / protein (e.g., Fc region) to create a fusion protein. In some embodiments, a variant is designed to be detectable and may comprise a detectable label and / or protein (e.g., a fluorescent label or an enzyme).

[00182] The variant antibodies or antigen-binding fragments described in this document can be generated using methods known in the art, including, but not limited to, mutagenesis. Petition 870250083106, dated 09 / 15 / 2025, pages 245 / 354 95 / 171 directed to the site, alanine scavenging mutagenesis, and PCR mutagenesis. Methods for mutagenesis and nucleotide sequence alterations are well known in the art. See, for example, Walker and Gaastra, eds. (1983) Techniques in Molecular Biology (MacMillan Publishing Company, New York); Kunkel, Proc. Natl. Acad. Sci. USA 82:488-492 (1985); Kunkel et al., Methods Enzymol. 54:367-382 (1987); Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual (Cold Spring Harbor, NY); US Pat. No. 4,873,192; and the references cited therein; incorporated herein by reference. Guidance on appropriate amino acid substitutions that do not affect the biological activity of the polypeptide of interest can be found in the Dayhoff et al. model. (1978) in Atlas of Protein Sequence and Structure (Natl. Biomed. Res. Found., Washington, DC), pp. 345-352, incorporated herein by reference in its entirety. the Dayhoff et al. modelThis uses the Point Accepted Mutation Amino Acid Similarity Matrix (PAM 250 matrix) to determine suitable conservative amino acid substitutions. Conservative substitutions, such as swapping one amino acid for another with similar properties, can be beneficial. Examples of conservative amino acid substitutions, as taught by the PAM 250 matrix of the Dayhoff et al. model, include, but are not limited to, Gly^Ala, ValMle^Leu, Asp^Glu, Lys^Arg, Asn^Gln, and Phe^Trp^Tyr.

[00183] In constructing variants of an anti-ILT7 binding molecule, for example, an antibody or antigen-binding fragment, variant or derivative thereof, modifications are made so that the variants continue to possess the desired properties, for example, being able to bind specifically to an ILT7 and, in certain embodiments, being able to inhibit IFN-alpha release and / or deplete pDCs in vivo. Obviously, any mutations made to the DNA encoding the variant polypeptide must not place the sequence out of the reading frame. In some embodiments, mutations made to the DNA do not create complementary regions that could produce mRNA secondary structure. Petition 870250083106, dated 09 / 15 / 2025, pages 246 / 354 96 / 171

[00184] In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment disclosed in this document may retain the ability to bind to ILT7 to a similar, equal, or greater extent than the original antibody or antigen-binding fragment. In some embodiments, the variant may be at least about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or more identical in amino acid sequence to the parental antibody or antigen-binding fragment. In certain embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises the amino acid sequence of the parental anti-ILT7 antibody or antigen-binding fragment with one or more conservative amino acid substitutions.Conservative amino acid substitutions are known in the art and include amino acid substitutions in which an amino acid with certain physical and / or chemical properties is exchanged for another amino acid that has the same or similar chemical or physical properties.

[00185] In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises the amino acid sequence of the original antibody or antigen-binding fragment with one or more non-conservative amino acid substitutions. In some embodiments, a variant of an anti-ILT7 antibody or antigen-binding fragment comprises the amino acid sequence of the original binding antibody or antigen-binding fragment with one or more non-conservative amino acid substitutions, wherein one or more non-conservative amino acid substitutions do not interfere with or inhibit one or more biological activities of the variant (e.g., ILT7 binding). In certain embodiments, one or more conservative amino acid substitutions and / or one or more non-conservative amino acid substitutions may enhance a biological activity of the variant, such that the biological activity of the functional variant is Petition 870250083106, dated 09 / 15 / 2025, pp. 247 / 354 97 / 171 increased compared to the original antibody or antigen-binding fragment.

[00186] In some embodiments, the variant has 1, 2, 3, 4, or 5 amino acid substitutions in CDRs (e.g., VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3) of the linker moiety.

[00187] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document are chemically modified naturally or by intervention. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments have been chemically modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protective / blocking groups, proteolytic cleavage, and / or binding to a cellular ligand or other protein. Any of the numerous chemical modifications can be performed by known techniques. The anti-ILT7 antibodies or antigen-binding fragments may comprise one or more amino acid analogs (including, for example, non-natural amino acids), as well as other modifications known in the art.

[00188] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments disclosed in this document are linked to at least one agent to form an antibody conjugate. The conjugate may be, for example, an antibody conjugated to another protein, carbohydrate, lipid, steroid, immunosuppressant, or mixed-fraction molecule(s). These antibody conjugates include, but are not limited to, modifications that involve linking the antibody to one or more polymers. For example, an antibody or antigen-binding fragment may be linked to one or more water-soluble polymers. Linking to a water-soluble polymer reduces the likelihood of the antibody or antigen-binding fragment precipitating in an aqueous environment, such as a physiological environment. A specialist in the field may select a suitable water-soluble polymer based on considerations that include, but are not limited to, whether the conjugate Petition 870250083106, dated 09 / 15 / 2025, pp. 248 / 354 The 98 / 171 polymer / antibody will be used in the treatment of a patient, and if so, the pharmacological profile of the antibody (e.g., half-life, dosage, activity, antigenicity, and / or other factors).

[00189] To increase the effectiveness of antibody molecules as diagnostic or therapeutic agents, it is conventional to link or covalently bind or complex at least one desired molecule or fraction. Such a molecule or fraction may be, but is not limited to, at least one effector or reporter molecule. Effector molecules comprise molecules that have a desired activity, for example, cytotoxic activity. Non-limiting examples of effector molecules that have been attached to antibodies include toxins, antitumor agents, therapeutic enzymes, radionuclides, antiviral agents, chelating agents, cytokines, growth factors, and oligo- or polynucleotides. In contrast, a reporter molecule is defined as any fraction that can be detected using an assay.Non-limiting examples of reporter molecules that have been conjugated to antibodies include enzymes, radiomarkers, haptens, fluorescent markers, phosphorescent molecules, chemiluminescent molecules, chromophores, photoaffinity molecules, colored particles or ligands, an enzyme (e.g., that catalyzes a colorimetric or fluorometric or bioluminescent reaction), a substrate, a solid matrix such as biotin. An antibody may comprise one, two, or more of any of these markers.

[00190] In some embodiments, anti-ILT7 antibodies or antigen-binding fragments described in this document are chemically modified naturally or by intervention. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments have been chemically modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protective / blocking groups, proteolytic cleavage, and / or binding to a cellular ligand or other protein. Any of the numerous chemical modifications can be performed by known techniques. The anti-ILT7 antibodies or antigen-binding fragments Petition 870250083106, dated 09 / 15 / 2025, pp. 249 / 354 99 / 171 may comprise one or more analogues of an amino acid (including, for example, non-natural amino acids), as well as other modifications known in the art.

[00191] Antibody conjugates can be used to deliver cytotoxic agents to target cells. Cytotoxic agents of this type can enhance antibody-mediated cytotoxicity and include fractions such as cytokines that directly or indirectly stimulate cell death, radioisotopes, chemotherapeutic drugs (including prodrugs), bacterial toxins (e.g., Pseudomonas exotoxin, diphtheria toxin, etc.), plant toxins (e.g., ricin, gelonin, etc.), chemical conjugates (e.g., maytansinoid toxins, calicheamicin, etc.), radioconjugates, enzyme conjugates (e.g., RNase conjugates, enzyme therapy / granzyme antibody-targeted prodrug) and the like.

[00192] Antibody conjugates are also used as diagnostic agents. In some embodiments, an anti-ILT7 antibody or antigen-binding fragment described in this document is conjugated to a detectable substance or molecule that allows the agent to be used for diagnosis and / or detection. A detectable substance may include, but is not limited to, enzymes; prosthetic groups (e.g., biotin and flavin(s)); fluorescent materials; bioluminescent materials, such as luciferase; radioactive materials; positron-emitting metals; and magnetic metal ions.

[00193] Antibody diagnostics generally fall into two classes: those for use in in vitro diagnostics, such as in a variety of immunoassays, and those for use in in vivo diagnostic protocols, generally known as “antibody-directed imaging.” Many suitable imaging agents are known in the art, as are methods for their attachment to antibodies (see, for example, U.S. Patents 5,021,236, 4,938,948, and 4,472,509). The imaging groups used may be paramagnetic ions, radioactive isotopes, fluorochromes, substances Petition 870250083106, dated 09 / 15 / 2025, pages 250 / 354 100 / 171 detectable by NMR, hyperpolarized molecules by MR, targeted ultrasound bubbles and X-ray imaging agents.

[00194] Paramagnetic ions contemplated for use as conjugates include chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), neodymium (III), samarium (III), ytterbium (III), gadolinium (III), vanadium (II), terbium (III), dysprosium (III), holmium (III), and / or erbium (III), with gadolinium being particularly preferred. Ions useful in other contexts, such as X-ray imaging, include, but are not limited to, lanthanum (III), gold (III), lead (II), and bismuth (III). Useful alternative isotopes are those used for hyperpolarized magnetic resonance imaging, such as carbon-13 and silica-29.

[00195] Radioactive isotopes contemplated for use in imaging and radiotherapy as conjugates or covalent incorporation include astatine-211, actinium-225, carbon-14, bismuth-212, chromium-51, chlorine-36, cobalt-57, cobalt-58, copper-64, copper-67, europium-152, fluorine-18, gallium-68, gallium-67, gold-198, hydrogen-3, iodine-123, iodine-125, iodine-131, indium-111, iron-52, iron-59, lead-212, lutetium-177, phosphorus-32, rhenium-186, rhenium-188, rubidium-82, rhodium-99, selenium-75, sulfur-35, samarium-153, Strontium-92, strontium-89, thallium-201, thorium-227, technetium-94m, technetium-99m, yttrium-86, yttrium-90, zirconium-86 and / or zirconium-89. F-18, Zr-89 and Cu-64 are often preferred for PET imaging. Lu-177, At-211 and Yt-90 are often preferred for radiotherapy. Radioactively labeled monoclonal antibodies and antibody fragments of the present disclosure can be produced according to methods well known in the art.For example, monoclonal antibodies can be iodinated by contact with sodium and / or potassium iodide and a chemical oxidizing agent, such as sodium hypochlorite, or an enzymatic oxidizing agent, such as lactoperoxidase. Monoclonal antibodies, according to the disclosure, can be labeled with technetium-99m by the ligand exchange process, for example, by reducing pertechnetate with stannous solution, chelating the reduced technetium on a Sephadex column, and applying the antibody to this column. Alternatively, direct labeling techniques can be used, for example... Petition 870250083106, dated 09 / 15 / 2025, pages 251 / 354 101 / 171 incubating pertechnetate, a reducing agent such as SNCl2, a buffer solution such as sodium-potassium phthalate solution, and the antibody. Intermediate functional groups incorporating chelating agents, which are frequently used to bind radioisotopes that exist as metal ions to an antibody, are diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), monomeric or dendrimeric 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), deferoxamine (DFO), or 1-hydroxy-2(1H)-pyridinone derivatives (e.g., 3,4,3-LI(1,2-HOPO) or HOPO).

[00196] The fluorescent markers contemplated for use as conjugates include Alexa 350, Alexa 430, AMCA, BODIPY 630 / 650, BODIPY 650 / 665, BODIPY-FL, BODIPY-R6G, BODIPY-TMR, BODIPY-TRX, Cascade Blue, cyanine (Cy3), Cy5,6-FAM, dansyl chloride, dichlorotriazylamine fluorescein, fluorescein isothiocyanate (FITC), HEX, 6-JOE, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, phycoerythrin, REG, Rhodamine Green, Rhodamine Red, Renografin, ROX, TAMRA, TET, tetramethylrhodamine isothiocyanate (TRITC), Texas Red and / or Umbelliferone.

[00197] Additional antibody types contemplated in this disclosure are those intended primarily for in vitro use, where the antibody is linked to a secondary binding ligand and / or an enzyme (an enzymatic tag) that will generate a colored product upon contact with a chromogenic substrate. Examples of suitable enzymes include beta-galactosidase, acetylcholinesterase, urease, alkaline phosphatase, hydrogen peroxidase (horseradish), or glucose oxidase. Preferred secondary binding ligands are biotin and avidin and streptavidin compounds.

[00198] Several methods are known in the art for the binding or conjugation of an antibody to its conjugate moiety. Some fixation methods involve the use of a metal chelate complex employing, for example, an organic chelating agent such as diethylenetriaminepentaacetic acid anhydride (DTPA); ethylenediaminetetraacetic acid; 1,4,7,10 Petition 870250083106, dated 09 / 15 / 2025, pages 252 / 354 102 / 171 monomeric or dendrimeric tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA); 1,4,7-triazacyclononano-1,4,7-triacetic acid (NOTA); DFO; HOPO; N-chloro-p-toluenesulfonamide; and / or antibody-linked tetrachloro-3α-6α-diphenylglucuryl-3 (US Patents 4,472,509 and 4,938,948). Monoclonal antibodies can also react with an enzyme in the presence of a coupling agent such as glutaraldehyde or periodate. Fluorescein-labeled conjugates are prepared in the presence of these coupling agents or by reaction with an isothiocyanate. In US Patent 4,938,948, breast tumor imaging is achieved using monoclonal antibodies, and detectable imaging fractions are linked to the antibody using ligands such as methyl-p-hydroxybenzimidate or N-succinimidyl-3-(4-hydroxyphenyl)propionate.

[00199] Another known method of specific molecule binding to antibodies involves the reaction of antibodies with hapten-based affinity markers. Essentially, hapten-based affinity markers react with amino acids at the antigen binding site, destroying that site and blocking the antigen-specific reaction.

[00200] Molecules containing azido groups can also be used to form covalent bonds with proteins via reactive nitrene intermediates generated by low-intensity ultraviolet light. In particular, 2- and 8-azido analogs of purine nucleotides have been used as site-directed photoprobes to identify nucleotide-binding proteins in crude cell extracts. 2- and 8-azido nucleotides have also been used to map nucleotide-binding domains of purified proteins and can be used as antibody-binding agents.

[00201] Also contemplated is the derivatization of immunoglobulins by the selective introduction of sulfhydryl groups into the Fc region of an immunoglobulin, using reaction conditions that do not alter the antibody binding site. Antibody conjugates produced according to this methodology are reported to have greater longevity. Petition 870250083106, dated 09 / 15 / 2025, pages 253 / 354 103 / 171 specificity and sensitivity (US Patent 5,196,066, incorporated herein by reference). The specific attachment of effector or reporter molecules, in which the reporter molecule is conjugated to a carbohydrate residue in the Fc region, has also been reported in the literature. This approach has been reported to produce promising antibodies in terms of diagnostics and therapy, which are currently under clinical evaluation.

[00202] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are conjugated to a steroid or an immunosuppressant. In some embodiments, the antibody or antigen-binding fragment is conjugated to a steroid or an immunosuppressant to form an ADC (antibody-drug conjugate). In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are conjugated to a steroid, which may be a corticosteroid. The corticosteroid may be, for example, dexamethasone, hydrocortisone, methylprednisolone, and prednisone.In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are conjugated to an immunosuppressant, which may be an antimalarial (such as hydroxychloroquine, chloroquine), an antimetabolite (such as methotrexate, azathioprine, mercaptopurine), a calcineurin inhibitor (such as cyclosporine, tacrolimus), mycophenolic acid, mycophenolate mofetil, thalidomide, or acitretin.

[00203] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are conjugated to a cytotoxic agent or fraction. In some embodiments, the antibody or antigen-binding fragment is conjugated to a cytotoxic agent to form an ADC (antibody-drug conjugate). In some embodiments, antibody-drug conjugates, or ADCs, are a class of highly potent biopharmaceutical drugs designed as targeted therapy. ADCs consist of an antibody (a whole mAb or an antibody fragment, such as an scFv) linked, via a stable chemical linker, with Petition 870250083106, dated 09 / 15 / 2025, pp. 254 / 354 104 / 171 labile bonds, to an active biological cytotoxic / antiviral payload or to a drug. Antibody-drug conjugates are examples of bioconjugates and immunoconjugates. By combining the unique targeting capabilities of monoclonal antibodies with cytotoxic drugs, ADCs allow for sensitive discrimination between healthy and diseased tissues. This means that, unlike traditional systemic approaches, ADCs target and attack the diseased cell, so that healthy cells are less severely affected.

[00204] In the development of ADC-based antitumor therapies, a warhead (e.g., a cellular toxin or cytotoxin) is coupled to an antibody that specifically targets a particular cellular marker (e.g., a protein that ideally can only be found inside or on diseased cells). Antibodies target these proteins in the body and bind to the surface of diseased cells. The biochemical reaction between the antibody and the target protein (antigen) triggers a signal in the target cell, which then absorbs or internalizes the antibody along with the cytotoxin. After the ADC is internalized, the cytotoxic drug is released and kills the cell or impairs cell replication. In other cases, the ligand is cleavable at the surface of the target cell or early endosomes, and as such, complete internalization is not required.Due to this targeting, ideally the medication should have fewer side effects and offer a wider therapeutic window than other agents.

[00205] In some embodiments, the cytotoxic fraction of ADCs possessing the anti-ILT7 antibodies or antigen-binding fragments described in this document is a chemotherapeutic agent including, but not limited to, methotrexate, adriamycin / doxorubicin, melphalan, mitomycin C, chlorambucil, duocarmycin, daunorubicin, pyrrolobenzodiazepines (PBDs), or other intercalating agents. In some embodiments, the cytotoxic fraction is a microtubule inhibitor, including, but not limited to, auristatins, maytansinoids (e.g., DM1 and DM4), and tubulisins. In some embodiments, the cytotoxic fraction is an enzymatically active toxin of origin. Petition 870250083106, dated 09 / 15 / 2025, pages 255 / 354 105 / 171 bacterial, fungal, plant or animal, or fragments thereof, including, but not limited to, diphtheria A chain, active non-binding fragments of diphtheria toxin, exotoxin A chain, ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, diantin proteins, Phytolacca americana proteins (PAPI, PAPII and PAP-S), Momordica charantia inhibitor, curcin, crotin, Saponaria officinalis inhibitor, gelonin, mitogellin, restrictocin, fenomycin, enomycin and trichothecenes. In some embodiments, an antibody or antigen-binding fragment is conjugated to one or more small molecule toxins, such as calicheamicins, maytansinoids, trichothecenes and CC1065.

[00206] A stable link between the antibody and the cytotoxic agent is a crucial aspect of an ADC. Linkers are based on chemical motifs, including disulfides, hydrazones, or peptides (cleavable) or thioethers (non-cleavable), and control the distribution and delivery of the cytotoxic agent to the target cell. Cleavable and non-cleavable linker types have proven safe in clinical and preclinical trials. The availability of better and more stable linkers has changed the function of the chemical linker. The type of linker, cleavable or non-cleavable, confers specific properties to the cytotoxic drug (e.g., anticancer drug). For example, a non-cleavable linker keeps the drug inside the cell. As a result, the entire antibody, linker, and cytotoxic agent enter the target cell, where the antibody is degraded to the amino acid level. The resulting complex—amino acid, linker, and cytotoxic agent—now becomes the active drug.In contrast, cleavable ligands are catalyzed by enzymes within or on the host cell, thus releasing the cytotoxic agent. Commonly used mechanisms for ligand cleavage are protease sensitivity, pH sensitivity, and glutathione sensitivity. Another type of cleavable ligand adds an extra molecule between the cytotoxic drug and the cleavage site. This ligation technology allows researchers to create ADCs with more flexibility without altering the cleavage kinetics. A novel peptide cleavage method based on degradation. Petition 870250083106, dated 09 / 15 / 2025, pages 256 / 354 Edman's 106 / 171 was also developed. Future directions in ADC development also include the development of site-specific conjugates (TDCs) to further improve stability and therapeutic index, as well as α-emitting immunoconjugates and antibody-conjugated nanoparticles.

[00207] An anti-ILT7 antibody or antigen-binding fragment described in this document may be attached to a solid support. These solid supports include, but are not limited to, glass, cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride, or polypropylene. In some embodiments, an immobilized anti-ILT7 antibody or antigen-binding fragment is used in an immunoassay. In some embodiments, an immobilized anti-ILT7 antibody or antigen-binding fragment is used in the purification of the target antigen (e.g., human ILT7). D. POLYNUCLEOTIDES AND VECTORS

[00208] Also provided in this document are polynucleotides encoding a polypeptide (e.g., an anti-ILT7 antibody or antigen-binding fragment) described in this document. The term “polynucleotide encoding a polypeptide” encompasses a polynucleotide that includes only coding sequences for the polypeptide, as well as a polynucleotide that includes additional coding and / or non-coding sequences. Disclosure polynucleotides may be in the form of RNA or DNA. DNA may be cDNA, genomic DNA, or synthetic DNA and may be double-stranded or single-stranded. Single-stranded DNA may be the coding strand or the non-coding (antisense) strand. Disclosure polynucleotides may be mRNA.

[00209] This document expressly contemplates polynucleotides encoding any anti-ILT7 antibody or antigen-binding fragment disclosed in this document. For illustrative purposes, in some embodiments, the polynucleotides provided in this document encode an anti-ILT7 antibody or antigen-binding fragment comprising (1) as defined by Kabat, (a) a variable region of Petition 870250083106, dated 09 / 15 / 2025, pages 257 / 354 107 / 171 light chain (VL) comprising VL CDR1, VL CDR2 and VL CDR3 having amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VL CDRs; and / or (b) a variable heavy chain (VH) region comprising VH CDR1, VH CDR2 and VH CDR3 having amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VH CDRs; or (2) as defined by Chothia, (a) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VL CDRs; and / or (b) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively;or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VH CDRs.

[00210] In some embodiments, the polynucleotides provided in this document encode an anti-ILT7 antibody or antigen-binding fragment comprising (a) a VL with at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH with at least 85%, at least 90%, at least 95%, at least 98%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 10. The polynucleotides may be in the form of DNA. The polynucleotides may be in the form of mRNA.

[00211] In some embodiments, the polynucleotides provided in this document encode an anti-ILT7 antibody or antigen-binding fragment disclosed in this document comprising a VL and a VH, wherein the VL comprises VL CDR1, CDR2 and CDR3 and the VH comprises VH CDR1, CDR2 and CDR3, and wherein the VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and VH CDR3 have the amino acid sequences of (1) SEQ ID NOs: Petition 870250083106, dated 09 / 15 / 2025, pp. 258 / 354 108 / 171 11, 12, 13, 14, 15 and 16, respectively; or (2) SEQ ID NOs: 11, 12, 13, 17, 18 and 16, respectively; or a variant of these having up to about 5 amino acid substitutions, additions and / or deletions in the CDRs. Polynucleotides may be in the form of DNA. Polynucleotides may be in the form of mRNA.

[00212] In some embodiments, the polynucleotides provided in this document encode an anti-ILT7 antibody or antigen-binding fragment disclosed in this document, comprising a VL and a VH, wherein VL and VH have the amino acid sequences of (1) SEQ ID NOs: 9 and 10, respectively; (2) SEQ ID NOs: 19 and 23, respectively; (3) SEQ ID NOs: 19 and 24, respectively; (4) SEQ ID NOs: 19 and 25, respectively; (5) SEQ ID NOs: 19 and 26, respectively; (6) SEQ ID NOs: 19 and 27, respectively; (7) SEQ ID NOs: 19 and 28, respectively; (8) SEQ ID NOs: 20 and 23, respectively; (9) SEQ ID NOs: 20 and 24, respectively; (10) SEQ ID NOs: 20 and 25, respectively; (11) SEQ ID NOs: 20 and 26, respectively; (12) SEQ ID NOs: 20 and 27, respectively; (13) SEQ ID NOs: 20 and 28, respectively; (14) SEQ ID NOs: 21 and 23, respectively; (15) SEQ ID NOs: 21 and 24, respectively; (16) SEQ ID NOs: 21 and 25, respectively; (17) SEQ ID NOs: 21 and 26, respectively;(18) SEQ ID NOs: 21 and 27, respectively; (19) SEQ ID NOs: 21 and 28, respectively; (20) SEQ ID NOs: 22 and 23, respectively; (21) SEQ ID NOs: 22 and 24, respectively; (22) SEQ ID NOs: 22 and 25, respectively; (23) SEQ ID NOs: 22 and 26, respectively; (24) SEQ ID NOs: 22 and 27, respectively; or (25) SEQ ID NOs: 22 and 28, respectively. Polynucleotides can be in the form of DNA. Polynucleotides can be in the form of mRNA.

[00213] In some embodiments, VL and VH are connected by a linker. The linker can be flexible or rigid. In some embodiments, the linker has the amino acid sequence (GGGGS)n, n=1, 2, 3, 4 or 5 (SEQ ID NO: 35). In some embodiments, the linker has the amino acid sequence (EAAAK)n, n=1, 2, 3, 4 or 5 (SEQ ID NO: 36). In some embodiments, the Petition 870250083106, dated 09 / 15 / 2025, pp. 259 / 354 109 / 171 ligand has the amino acid sequence (PA)nP, n=1, 2, 3, 4 or 5 (SEQ ID NO: 37).

[00214] This disclosure also provides variants of the polynucleotides described in this document, wherein the variants encode, for example, fragments, analogs and / or derivatives of an anti-ILT7 antibody or antigen-binding fragment disclosed in this document. In some embodiments, this disclosure provides a polynucleotide with a nucleotide sequence that is at least about 80% identical, at least about 85% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical or at least about 99% identical to a polynucleotide sequence encoding an anti-ILT7 antibody or antigen-binding fragment described in this document.In some embodiments, the present disclosure provides a polynucleotide with a nucleotide sequence that is at least about 80% identical, at least about 85% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, or at least about 99% identical to a polynucleotide sequence encoding an anti-ILT7 antibody or antigen-binding fragment described in this document.

[00215] As used in this document, the phrase “a polynucleotide with a nucleotide sequence at least about 95% identical to a reference polynucleotide sequence” means that the nucleotide sequence of the polynucleotide is identical to a reference sequence, except that the reference polynucleotide sequence may include up to five point mutations for every 100 nucleotides in the reference nucleotide sequence. In other words, to obtain a polynucleotide with a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or replaced by another nucleotide, or a number of Petition 870250083106, dated 09 / 15 / 2025, pp. 260 / 354 110 / 171 nucleotides, up to 5% of the total nucleotides in the reference sequence, can be inserted into the reference sequence. These reference sequence mutations can occur at the 5' or 3' terminal positions of the reference nucleotide sequence, or anywhere between these terminal positions, interspersed individually between nucleotides in the reference sequence, or in one or more contiguous groups within the reference sequence.

[00216] Polynucleotide variants can contain alterations in coding regions, non-coding regions, or both. In some embodiments, a polynucleotide variant contains alterations that produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. In some embodiments, a polynucleotide variant comprises silent substitutions that do not result in any alteration in the amino acid sequence of the polypeptide (due to the degeneracy of the genetic code). Polynucleotide variants can be produced for various reasons, for example, to optimize codon expression for a specific host (e.g., altering codons in human mRNA to those preferred by a bacterial host, such as E. coli). In some embodiments, a polynucleotide variant comprises at least one silent mutation in a non-coding or coding region of the sequence.

[00217] In some embodiments, a polynucleotide variant is produced to modulate or alter the expression (or expression levels) of the encoded polypeptide. In some embodiments, a polynucleotide variant is produced to increase the expression of the encoded polypeptide. In some embodiments, a polynucleotide variant is produced to decrease the expression of the encoded polypeptide. In some embodiments, a polynucleotide variant has increased expression of the encoded polypeptide compared to a parental polynucleotide sequence. In some embodiments, a polynucleotide variant has decreased expression of the Petition 870250083106, dated 09 / 15 / 2025, pp. 261 / 354 111 / 171 encoded polypeptide compared to a parental polynucleotide sequence.

[00218] In some embodiments, a polynucleotide comprises the coding sequence of a polypeptide (e.g., an antibody) fused in the same reading frame to a polynucleotide that assists in the expression and secretion of a polypeptide from a host cell (e.g., a leader sequence that functions as a secretory sequence to control the transport of a polypeptide). The polypeptide may have the leader sequence cleaved by the host cell to form a “mature” form of the polypeptide.

[00219] In some embodiments, a polynucleotide comprises the coding sequence of a polypeptide (e.g., an antibody) fused in the same reading frame to a marker or label sequence. For example, in some embodiments, a marker sequence is a hexahistidine label (HIS label) (SEQ ID NO: 65) that allows for efficient purification of the polypeptide fused to the marker. In some embodiments, a marker sequence is a hemagglutinin (HA) label derived from the influenza hemagglutinin protein when a mammalian host (e.g., COS-7 cells) is used. In some embodiments, the marker sequence is a FLAG™ label. In some embodiments, a marker is used in conjunction with other markers or labels.

[00220] In some embodiments, a polynucleotide is isolated. In some embodiments, a polynucleotide is substantially pure.

[00221] Vectors and cells comprising the polynucleotides described in this document are also provided. In some embodiments, vectors comprising a polynucleotide provided in this document are provided in this document. The vectors may be expression vectors. In some embodiments, the vectors provided in this document comprise a polynucleotide encoding an anti-ILT7 antibody or antigen-binding fragment described in this document. In some embodiments, the vectors Petition 870250083106, dated 09 / 15 / 2025, pp. 262 / 354 112 / 171 provided in this document comprise a polynucleotide encoding a polypeptide that is part of an anti-ILT7 antibody or antigen-binding fragment described in this document.

[00222] In some embodiments, recombinant expression vectors are provided in this document, which can be used to amplify and express a polynucleotide encoding an anti-ILT7 antibody or antigen-binding fragment described in this document. For example, a recombinant expression vector may be a replicable DNA construct that includes synthetic or cDNA-derived DNA fragments encoding a polypeptide chain of an anti-ILT7 antibody, operatively linked to suitable transcriptional and / or translational regulatory elements derived from mammalian, microbial, viral, or insect genes. In some embodiments, a viral vector is used. DNA regions are “operatively linked” when they are functionally related to each other.For example, a promoter is operatively linked to a coding sequence if it controls the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned to allow translation. In some embodiments, the structural elements intended for use in certain expression systems include a leader sequence that allows extracellular secretion of the translated protein by a host cell. In some embodiments, in situations where the recombinant protein is expressed without a leader or transport sequence, a polypeptide may include an N-terminal methionine residue.

[00223] A wide variety of host / expression vector combinations can be employed. Useful expression vectors for eukaryotic hosts include, for example, vectors comprising expression control sequences of SV40, bovine papillomavirus, adenovirus, and cytomegalovirus. Useful expression vectors for bacterial hosts include known bacterial plasmids, such as E. coli plasmids, including pCR1, pBR322, pMB9 and their derivatives, and larger plasmids. Petition 870250083106, dated 09 / 15 / 2025, pp. 263 / 354 113 / 171 host range, such as M13 and other single-stranded filamentous DNA phages. In some embodiments, an anti-ILT7 antibody or antigen-binding fragment described in this document is expressed from one or more vectors.

[00224] Host cells comprising vectors described herein are provided in this document. In some embodiments, the host cells are used for recombinant expression of the anti-ILT7 antibodies described herein. The host cells may include prokaryotes, yeast cells, insect cells, or higher eukaryotic cells under the control of appropriate promoters. Cloning and expression vectors suitable for use with bacterial, fungal, yeast, and mammalian cell hosts, as well as methods of protein production, including antibody production, are well known in the art.

[00225] Examples of suitable mammalian host cells include, but are not limited to, COS-7 (derived from monkey kidney), L-929 (derived from murine fibroblast), C127 (derived from murine mammary tumor), 3T3 (derived from murine fibroblast), CHO (derived from Chinese hamster ovary), HeLa (derived from human cervical cancer), BHK (derived from hamster renal fibroblast), HEK-293 (derived from human embryonic kidney), and variants thereof. Mammalian expression vectors may comprise non-transcribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other non-transcribed 5' or 3' flanking sequences and untranslated 5' or 3' sequences such as necessary ribosome binding sites, a polyadenylation site, splicing donor and acceptor sites, and transcriptional termination sequences.The expression of recombinant proteins in insect cell culture systems (e.g., baculovirus) also offers a robust method for producing correctly folded and biologically functional proteins. Baculovirus systems for protein production. Petition 870250083106, dated 09 / 15 / 2025, pp. 264 / 354 114 / 171 heterologous molecules in insect cells are well known to those versed in the technique.

[00226] This disclosure also provides host cells comprising the polypeptides described herein, polynucleotides encoding polypeptides described herein, or vectors comprising such polynucleotides. In some embodiments, host cells comprising a vector comprising a polynucleotide disclosed herein are provided herein. In some embodiments, the host cells provided herein comprise a vector comprising a polynucleotide encoding an anti-ILT7 antibody or antigen-binding fragment described herein. In some embodiments, the host cells provided herein comprise a vector comprising a polynucleotide encoding a polypeptide that is part of an anti-ILT7 antibody or antigen-binding fragment described herein.In some embodiments, the host cells provided in this document comprise a polynucleotide encoding an anti-ILT7 antibody or antigen-binding fragment described in this document. In some embodiments, the cells produce the anti-ILT7 antibodies or antigen-binding fragments described in this document. E. MANUFACTURING METHODS

[00227] This document also provides methods for manufacturing anti-ILT7 antibodies and antigen-binding fragments thereof, including, but not limited to, monoclonal antibodies, polyclonal antibodies, synthetic antibodies, human antibodies, humanized antibodies, and antigen-binding fragments thereof.

[00228] Antibody production methods are well known in the art. See, for example, Harlow et al., Antibodies: A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2nd ed. 1988); Hammerling et al., in: Monoclonal Antibodies and T-Cell Hybridomas 563 681 (Elsevier, NY, 1981), each of which is incorporated herein by reference in its Petition 870250083106, dated 09 / 15 / 2025, pages 265 / 354 115 / 171 totality. In some embodiments, monoclonal antibodies are prepared using hybridoma methods known to a specialist in the field. For example, using a hybridoma method, a mouse, rat, rabbit, hamster, or other suitable host animal is immunized as described above. In some embodiments, lymphocytes are immunized in vitro. In some embodiments, the immunizing antigen is a human protein or a fragment thereof. In some embodiments, the immunizing antigen is a human protein or a fragment thereof.

[00229] After immunization, lymphocytes are isolated and fused with a suitable myeloma cell line using, for example, polyethylene glycol. Hybridoma cells are selected using specialized media as known in the art, and unfused lymphocytes and myeloma cells do not survive the selection process. Hybridomas that produce monoclonal antibodies directed to a chosen antigen can be identified by a variety of methods, including but not limited to immunoprecipitation, immunoblotting, and in vitro ligation assays (e.g., flow cytometry, FACS, ELISA, SPR (e.g., Biacore), and radioimmunoassay). Once hybridoma cells producing antibodies with the desired specificity, affinity, and / or activity are identified, clones can be subcloned by limiting dilution or other techniques. Hybridomas can be propagated in vitro using standard methods or in vivo as ascites tumors in an animal.Monoclonal antibodies can be purified from culture media or ascitic fluid according to standard methods in the art, including, but not limited to, affinity chromatography, ion-exchange chromatography, gel electrophoresis, and dialysis.

[00230] In some embodiments, monoclonal antibodies are produced using recombinant DNA techniques, as known to a person skilled in the art. For example, the polynucleotides encoding an antibody are isolated from mature B cells or hybridoma cells, such as by RT-PCR using oligonucleotide primers that specifically amplify Petition 870250083106, dated 09 / 15 / 2025, pp. 266 / 354 116 / 171 the genes encoding the antibody heavy and light chains, and their sequence is determined using standard techniques. The isolated polynucleotides encoding the heavy and light chains are then cloned into suitable expression vectors that produce the monoclonal antibodies when transfected into host cells, such as E. coli, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that otherwise do not produce immunoglobulin proteins.

[00231] Antibody polynucleotides or antigen-binding fragments provided in this document can be prepared, manipulated, and / or expressed using any of the well-established techniques known and available in the art. In some embodiments, antibody polynucleotides or antigen-binding fragments provided in this document can be prepared recombinantly. Many vectors can be used. Examples of vectors are plasmids, autonomously replicating sequences, and transposable elements. Exemplary transposon systems, such as Sleeping Beauty and PiggyBac, which can be stably integrated into the genome, can be used (e.g., Ivics et al., Cell, 91(4): 501-510 (1997); Cadinanos et al., Nucleic Acids Research, 35(12): e87 (2007)).Additional exemplary vectors include, but are not limited to, plasmids, phagemids, cosmids, artificial chromosomes such as yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC), or P1-derived artificial chromosome (PAC), bacteriophages such as lambda phage or M13 phage, and animal viruses. Examples of categories of animal viruses useful as vectors include, but are not limited to, retroviruses (including lentiviruses), adenoviruses, adeno-associated viruses, herpesviruses (e.g., herpes simplex virus), poxviruses, baculoviruses, papillomaviruses, and papovaviruses (e.g., SV40). Examples of expression vectors are the pCl-neo vectors (Promega) for expression in mammalian cells; pLenti4 / V5-DEST™, pLenti6 / V5-DEST™, and pLenti6.2 / V5GW / lacZ (Invitrogen) for lentivirus-mediated gene transfer and expression in mammalian cells. Petition 870250083106, dated 09 / 15 / 2025, pp. 267 / 354 117 / 171

[00232] In some embodiments, the vector is an episomal vector or a vector that is maintained extrachromosomally. As used in this document, the term “episomal” refers to a vector that is capable of replicating without integration into the host’s chromosomal DNA and without gradual loss from a dividing host cell, which also means that said vector replicates extrachromosomally or episomally. The vector is designed to harbor the sequence encoding the origin of DNA replication or “ori” of a herpes lymphotropic virus or a gamma herpesvirus, an adenovirus, SV40, a bovine papillomavirus, or a yeast, specifically an origin of replication of a herpes lymphotropic virus or a gamma herpesvirus corresponding to the EBV oriP. In some forms, the lymphotropic herpes virus is the Epstein-Barr virus (EBV), the Kaposi's sarcoma herpes virus (KSHV), the herpes saimiri virus (HS), or the Marek's disease virus (MDV).Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) are also examples of gamma herpesviruses. Typically, the host cell understands the viral replication transactivator protein that activates replication.

[00233] “Expression control sequences,” “control elements,” or “regulatory sequences” present in an expression vector are those untranslated regions of the vector—origin of replication, selection cassettes, promoters, enhancers, translation initiation signals (Shine Dalgarno sequence or Kozak sequence), introns, a polyadenylation sequence, 5' and 3' untranslated regions—that interact with host cellular proteins to perform transcription and translation. Such elements can vary in their strength and specificity. Depending on the vector system and the host used, any number of suitable transcription and translation elements, including ubiquitous promoters and inducible promoters, can be used.

[00234] Illustrative ubiquitous expression control sequences that may be used in this disclosure include, but are not limited to, an immediate early promoter of cytomegalovirus (CMV), a promoter of simian virus 40 (SV40) (e.g., early or late), a promoter of Petition 870250083106, dated 09 / 15 / 2025, pp. 268 / 354 118 / 171 Moloney murine leukemia virus (MoMLV) LTR, a Rous sarcoma virus (RSV) LTR, a herpes simplex virus (HSV) promoter (thymidine kinase), vaccinia virus H5, P7.5 and P11 promoters, an elongation factor 1-alpha (EF1a) promoter, early growth response 1 (EGR1), ferritin H (FerH), ferritin L (FerL), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), eukaryotic translation initiation factor 4A1 (EIF4A1), 70 kDa heat shock protein 5 (HSPA5), 90 kDa heat shock protein Beta, member 1 (HSP90B1), 70 kDa heat shock protein (HSP70), β-kinesin (β-KIN), the human ROSA 26 locus (Irions et al., Nature Biotechnology 25, 1477-1482 (2007)), a ubiquitin C (UBC) promoter, a phosphoglycerate kinase-1 (PGK) promoter, a cytomegalovirus enhancer / chicken β-actin (CAG) promoter, and a β-actin promoter.

[00235] Illustrative examples of inducible promoters / systems include, but are not limited to, steroid-inducible promoters, such as promoters for genes encoding glucocorticoid or estrogen receptors (inducible by treatment with the corresponding hormone), metallothionein promoter (inducible by treatment with various heavy metals), MX-1 promoter (inducible by interferon), the mifepristone-regulated “GeneSwitch” system (Sirin et al., 2003, Gene, 323:67), the coumate-inducible gene switch (WO 2002 / 088346), tetracycline-dependent regulatory systems, etc. The anti-ILT7 antibodies or antigen-binding fragments described in this document can be produced by any method known in the art, including chemical synthesis and recombinant expression techniques.Unless otherwise indicated, the practice of the invention employs conventional techniques in molecular biology, microbiology, genetic analysis, recombinant DNA, organic chemistry, biochemistry, PCR, oligonucleotide synthesis and modification, nucleic acid hybridization, and related fields within the skill of the technique.

[00236] The polypeptides described in this document can be prepared using a wide variety of techniques known in the art, Petition 870250083106, dated 09 / 15 / 2025, pp. 269 / 354 119 / 171 including the use of hybridoma and recombinant technologies, or a combination thereof. In some embodiments, a recombinant expression vector is used to express a polynucleotide encoding a polypeptide described in this document. For example, a recombinant expression vector may be a replicable DNA construct that includes synthetic or cDNA-derived DNA fragments encoding a polypeptide operatively linked to suitable transcriptional and / or translational regulatory elements derived from mammalian, microbial, viral, or insect genes. In some embodiments, polypeptide-coding sequences disclosed in this document may be linked to such expression vectors for their expression in mammalian cells. In some embodiments, a viral vector is used. DNA regions are “operatively linked” when they are functionally related to each other.For example, a promoter is operatively linked to a coding sequence if it controls the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned to allow translation. In some embodiments, the structural elements intended for use in yeast expression systems include a leader sequence that allows extracellular secretion of translated protein by a host cell. In some embodiments, in situations where the recombinant protein is expressed without a leader or transport sequence, a polypeptide may include an N-terminal methionine residue.

[00237] A wide variety of host / expression vector combinations can be employed. Suitable host cells for expression include prokaryotes, yeast cells, insect cells, or higher eukaryotic cells under the control of appropriate promoters. Cloning and expression vectors suitable for use with bacterial, fungal, yeast, and mammalian cell hosts, as well as methods of protein production, including antibody production, are well known in the art. Useful expression vectors for hosts Petition 870250083106, dated 09 / 15 / 2025, pp. 270 / 354 120 / 171 bacterial plasmids include known bacterial plasmids, such as E. coli plasmids, including pCR1, pBR322, pMB9 and their derivatives, and plasmids with a wider host range, such as M13 and other single-stranded filamentous DNA phages.

[00238] Useful expression vectors for eukaryotic hosts include, for example, vectors comprising expression control sequences of SV40, bovine papillomavirus, adenovirus, and cytomegalovirus. Examples of suitable mammalian host cell lines include, but are not limited to, COS-7 (derived from monkey kidney), L-929 (derived from murine fibroblast), C127 (derived from murine mammary tumor), 3T3 (derived from murine fibroblast), CHO (derived from Chinese hamster ovary), HeLa (derived from human cervical cancer), BHK (derived from hamster kidney fibroblast), HEK-293 cell lines (derived from human embryonic kidney), and variants thereof.Mammalian expression vectors may comprise non-transcribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other non-transcribed 5' or 3' flanking sequences and untranslated 5' or 3' sequences such as necessary ribosome binding sites, a polyadenylation site, splicing donor and acceptor sites, and transcriptional termination sequences. The expression of recombinant proteins in insect cell culture systems (e.g., baculovirus) also offers a robust method for producing correctly folded and biologically functional proteins. Baculovirus systems for the production of heterologous proteins in insect cells are well known to those skilled in the art.

[00239] To produce anti-ILT7 antibodies and antigen-binding fragments that are afucosylated, host cells that (1) overexpress N-acetylglucosaminyltransferase III (GnTIII), (2) lack α-1,6-fucosyltransferase (FUT8), or (3) have low fucose content, or any combination of (1)-(3), may be used. In some embodiments, they are Petition 870250083106, dated 09 / 15 / 2025, pp. 271 / 354 121 / 171 host cells overexpressing N-acetylglucosaminyltransferase III (GnTIII) are used in this document. In some embodiments, host cells lacking 1,6-fucosyltransferase (FUT8) are used in this document. In some embodiments, host cells with low fucose content are used in this document. In some embodiments, CHO host cells are used.

[00240] Peptides can be synthesized, in whole or in part, using chemical methods (see, for example, Caruthers (1980). Nucleic Acids Res. Symp. Ser. 215; Horn (1980); and Banga, AK, Therapeutic Peptides and Proteins, Formulation, Processing and Delivery Systems (1995) Technomic Publishing Co., Lancaster, PA). Peptide synthesis can be performed using various solid-phase techniques (see, for example, Roberge, Science 269:202 (1995); Merrifield, Methods. Enzymol. 289:3 (1997)) and automated synthesis can be achieved, for example, using the ABI 431A peptide synthesizer (Perkin Elmer) according to the manufacturer's instructions. Peptides can also be synthesized using combinatorial methodologies. Synthetic residues and polypeptides can be synthesized using a variety of procedures and methodologies known in the art (see, for example, Organic Syntheses Collective Volumes, Gilman, et al. (Eds.) John Wiley & Sons, Inc., NY).Modified peptides can be produced by chemical modification methods (see, for example, Belousov, Nucleic Acids Res. 25:3440 (1997); Frenkel, Free Radic. Biol. Med. 19:373 (1995); and. Blommers, Biochemistry 33:7886 (1994)). Variations, derivatives, substitutions, and modifications in peptide sequences can also be made using methods such as oligonucleotide-mediated (site-directed) mutagenesis, alanine screening, and PCR-based mutagenesis. Site-directed mutagenesis (Carter et al., Nucl. Acids Res., 13:4331 (1986); Zoller et al., Nucl. Acids Res. 10:6487 (1987)), cassette mutagenesis (Wells et al., Gene 34:315 (1985)), restriction selection mutagenesis (Wells et al., Philos. Trans. R. Soc. London SerA 317:415 (1986)), and other techniques can be performed on DNA. Petition 870250083106, dated 09 / 15 / 2025, pp. 272 / 354 122 / 171 cloned to produce peptide sequences of invention, variants, fusions and chimeras, and variations, derivatives, substitutions and modifications thereof.

[00241] For in vivo use of antibodies in humans, it may be preferable to use human antibodies. Completely human antibodies are particularly desirable for therapeutic treatment of humans. Human antibodies can be produced by a variety of methods known in the art, including phage display methods using antibody libraries derived from human immunoglobulin sequences, including improvements on these techniques. See also U.S. Patent Nos. 4,444,887 and 4,716,111; and PCT publications WO 98 / 46645, WO 98 / 50433, WO 98 / 24893, WO 98 / 16654, WO 96 / 34096, WO 96 / 33735 and WO 91 / 10741; each of which is incorporated herein by reference in its entirety. A human antibody can also be an antibody in which the heavy and light chains are encoded by a nucleotide sequence derived from one or more sources of human DNA.

[00242] In some embodiments, an anti-ILT7 antibody or antigen-binding fragment is a human antibody or antigen-binding fragment. Human antibodies can be prepared using various techniques known in the art. In some embodiments, human antibodies are generated from immortalized and immunized human B lymphocytes in vitro. In some embodiments, human antibodies are generated from lymphocytes isolated from an immunized individual. In either case, cells that produce an antibody directed against a target antigen can be generated and isolated. In some embodiments, a human antibody is selected from a phage library, wherein that phage library expresses human antibodies. Alternatively, phage display technology can be used to produce human antibodies and antibody fragments in vitro from immunoglobulin variable region gene repertoires of non-immunized donors.Techniques for generating and using antibody phage libraries are well known in the field. Since... Petition 870250083106, dated 09 / 15 / 2025, pp. 273 / 354 123 / 171 once antibodies are identified, affinity maturation strategies known in the art, including but not limited to chain shuffling and site-directed mutagenesis, can be employed to generate higher-affinity human antibodies. In some embodiments, human antibodies are produced in transgenic mice containing human immunoglobulin loci. After immunization, these mice can produce the full repertoire of human antibodies in the absence of endogenous immunoglobulin production.

[00243] Human antibodies can also be produced using transgenic mice that are unable to express functional endogenous immunoglobulins but can express human immunoglobulin genes. For example, human heavy and light chain immunoglobulin gene complexes can be introduced randomly or by homologous recombination into mouse embryonic stem cells. Alternatively, the human variable region, constant region, and diversity region can be introduced into mouse embryonic stem cells in addition to the human heavy and light chain genes. The mouse heavy and light chain immunoglobulin genes can become non-functional separately or simultaneously with the introduction of human immunoglobulin loci by homologous recombination.For example, it has been described that homozygous deletion of the antibody heavy chain binding region (JH) gene in chimeric and germline mutant mice results in complete inhibition of endogenous antibody production. Modified embryonic stem cells are expanded and microinjected into blastocysts to produce chimeric mice. The chimeric mice are then reared to produce homozygous offspring expressing human antibodies. The transgenic mice are immunized in the normal manner with a selected antigen, for example, all or part of a polypeptide of the invention. For example, anti-ILT7 antibodies directed against the human antigen ILT7 may be used. Petition 870250083106, dated 09 / 15 / 2025, pp. 274 / 354 124 / 171 obtained from transgenic mice immunized using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation and subsequently undergo class switching and somatic mutation. Thus, using this technique, it is possible to produce therapeutically useful IgG, IgA, IgM, and IgE antibodies, including, but not limited to, IgG1 (gamma 1) and IgG3. For an overview of this technology for the production of human antibodies, see Lonberg and Huszar (Int. Rev. Immunol., 13:65-93 (1995)). For a detailed discussion of this technology for the production of human antibodies and human monoclonal antibodies and protocols for the production of such antibodies, see, for example, PCT Publications Nos. WO 98 / 24893, WO 96 / 34096, and WO 96 / 33735; and U.S. Patent Nos. 5,413,923; 5,625,126; 5,633,425; 5,569,825; 5,661,016; 5,545,806; 5,814,318; and 5,939,598, each of which is incorporated by reference herein in its entirety. In addition, companies such as Abgenix, Inc. (Fremont, California) and Genpharm (San Jose, California) may be contracted to supply human antibodies targeted against a selected antigen using technology similar to that described above. For a specific discussion of the transfer of a human germline immunoglobulin gene array into germline mutant mice that will result in the production of human antibodies upon antigen challenge, see, for example, Jakobovits et al., Proc. Natl. Acad. Sci. USA, 90:2551 (1993); Jakobovits et al., Nature, 362:255-258 (1993); Bruggermann et al., Year in Immunol., 7:33 (1993); and Duchosal et al., Nature, 355:258 (1992).

[00244] Human antibodies can also be derived from phage display libraries (Hoogenboom et al., J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581-597 (1991); Vaughan et al., Nature Biotech., 14:309 (1996)). Phage display technology (McCafferty et al., Nature, 348:552-553 (1990)) can be used to produce human antibodies and antibody fragments in vitro from domain gene repertoires. Petition 870250083106, dated 09 / 15 / 2025, pages 275 / 354 125 / 171 variable (V) immunoglobulin from non-immunized donors. According to this technique, the V domain genes of the antibody are cloned into a frame into a major or minor gene of the coat protein of a filamentous bacteriophage, such as M13 or fd, and displayed as functional antibody fragments on the surface of the phage particle. Because the filamentous particle contains a single-stranded DNA copy of the phage genome, selections based on the functional properties of the antibody also result in the selection of the gene encoding the antibody that exhibits those properties. Thus, the phage mimics some of the properties of the B cell. Phage display can be performed in a variety of formats; for a review, see, for example, Johnson and Chiswell, Current Opinion in Structural Biology 3:564-571 (1993). Several sources of V gene segments can be used for phage display. Clackson et al.Nature, 352: 624-628 (1991) isolated a variety of anti-oxazolone antibodies from a small combinatorial random library of V genes derived from the spleens of non-immunized mice. A repertoire of V genes from non-immunized human donors can be constructed and antibodies to a diverse range of antigens (including autoantigens) can be isolated essentially by following the techniques described by Marks et al., J. Mol. Biol., 222: 581-597 (1991), or Griffith et al., EMBO J., 12: 725-734 (1993). See also U.S. Patent Nos. 5,565,332 and 5,573,905, each of which is incorporated herein by reference in its entirety.

[00245] Human antibodies can also be generated by activated B cells in vitro (see, US Patent Nos. 5,567,610 and 5,229,275, each of which is incorporated herein by reference in its entirety). Human antibodies can also be generated in vitro using hybridoma techniques, such as, but not limited to, that described by Roder et al. (Methods Enzymol., 121:140-167 (1986)).

[00246] Alternatively, in some embodiments, a non-human antibody is humanized, where specific sequences or regions of the antibody are modified to increase similarity to a human antibody. Petition 870250083106, dated 09 / 15 / 2025, pp. 276 / 354 126 / 171 produced naturally in a human being. In some embodiments, the portion of the antigen-binding domain is humanized. Several methods for generating humanized antibodies are known in the art. Methods are known in the art for achieving high-affinity binding with humanized antibodies. A non-limiting example of such a method is hypermutation of the variable region and selection of cells expressing such high-affinity antibodies (affinity maturation). In addition to the use of display libraries, the specified antigen (e.g., recombinant ILT7 or an epitope thereof) can be used to immunize a non-human animal, e.g., a rodent. In certain embodiments, rodent antigen-binding fragments (e.g., mouse antigen-binding fragments) can be generated and isolated using methods known in the art and / or disclosed in this document.In some modalities, a mouse can be immunized with an antigen (for example, recombinant ILT7 or an epitope thereof).

[00247] A humanized antibody can be produced using techniques that include, but are not limited to, CDR grafting (see, for example, European Patent No. EP 239,400; International Publication No. WO 91 / 09967; and US Patent Nos. 5,225,539, 5,530,101 and 5,585,089, each of which is incorporated herein in its entirety by reference), coating or recoating (see, for example, European Patents Nos. EP 592,106 and EP 519,596; Padlan, 1991, Molecular Immunology, 28(4 / 5):489-498; Studnicka et al., 1994, Protein Engineering, 7(6):805-814; and Roguska et al., 1994, PNAS, 91:969-973, each of which is incorporated herein in its entirety by reference), chain scrambling (see, for example, U.S. Patent No. 5,565,332, which is incorporated herein in its entirety by reference), and techniques disclosed in, for example, U.S. Patent Application Publication No. US2005 / 0042664, U.S. Patent Application Publication No.° US2005 / 0048617, US Patent No. 6,407,213, US Patent No. 5,766,886, International Publication No. WO 9317105, Tan et al., J. Immunol., 169:1119-25 (2002), Caldas et al., Protein Eng., 13(5):353-60 (2000), Morea et. Petition 870250083106, dated 09 / 15 / 2025, pp. 277 / 354 127 / 171 al., Methods, 20(3):267-79 (2000), Baca et al., J. Biol. Chem., 272(16):10678-84 (1997), Roguska et al., Protein Eng., 9(10):895-904 (1996), Couto et al., Câncer Res., 55 (23 Supp):5973s-5977s (1995), Couto et al., Câncer Res., 55(8):171722 (1995), Sandhu JS, Gene, 150(2):409-10 (1994), and Pedersen et al., J. Mol. Biol., 235(3):959-73 (1994), each of which is incorporated herein in full by reference. Frequently, structural residues in the structure regions can be replaced by the corresponding residue of the CDR donor antibody to alter, preferably improve, antigen binding. These structural substitutions are identified by well-known methods in the art, for example, by modeling the interactions of CDR and structural residues to identify structural residues important for antigen binding and by sequence comparison to identify unusual structural residues at specific positions.(See, for example, Queen et al., U.S. Patent 5,585,089; and Riechmann et al., 1988, Nature, 332:323, which are incorporated herein by reference in their entirety.)

[00248] A humanized antibody has one or more amino acid residues introduced into it from a non-human source. These non-human amino acid residues are often called “import” residues, which are typically taken from a variable “import” domain. Thus, humanized antibodies comprise one or more CDRs from non-human immunoglobulin molecules and human structural regions. Antibody humanization is well known in the art and can essentially be performed following the method of Winter and colleagues (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), replacing rodent CDRs or CDR sequences with the corresponding sequences of a human antibody, i.e., CDR grafting (EP 239,400; PCT Publication No. WO 91 / 09967; and US Patent Nos. 4,816,567; 6,331,415; 5,225,539; 5,530,101; 5,585,089; 6,548).640, the contents of which are incorporated herein by reference in full). In such humanized chimeric antibodies,. Petition 870250083106, dated 09 / 15 / 2025, pp. 278 / 354 128 / 171 substantially less than an intact human variable domain has been replaced by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are replaced by residues from analogous sites in rodent antibodies. Antibody humanization can also be achieved by coating or recapping (EP 592,106; EP 519,596; Padlan, 1991, Molecular Immunology, 28(4 / 5):489-498; Studnicka et al., Protein Engineering, 7(6):805-814 (1994); and Roguska et al., PNAS, 91:969-973 (1994)) or chain scrambling (US Patent No. 5,565,332), the contents of which are incorporated herein by reference in full.

[00249] The choice of human variable domains, both light and heavy, to be used in the production of humanized antibodies is to reduce antigenicity. According to the so-called “best fit” method, the variable domain sequence of a rodent antibody is screened against the entire library of known human variable domain sequences. The human sequence closest to that of the rodent is then accepted as the human structure (RF) for the humanized antibody (Sims et al., J. Immunol., 151:2296 (1993); Chothia et al., J. Mol. Biol., 196:901 (1987), the contents of which are incorporated herein by reference in full). Another method uses a specific structure derived from the consensus sequence of all human antibodies of a specific subset of light or heavy chains. The same structure can be used for several different humanized antibodies (Carter et al., Proc. Natl. Acad. Sci. USA, 89:4285 (1992); Presta et al., J. Immunol., 151:2623 (1993), the content of which is incorporated herein by reference in its entirety).

[00250] Antibodies can be humanized while maintaining high affinity for the target antigen and other favorable biological properties. For example, humanized antibodies can be prepared by a process of analyzing parental sequences and various conceptual humanized products. Petition 870250083106, dated 09 / 15 / 2025, pp. 279 / 354 129 / 171 using three-dimensional models of parental and humanized sequences. Three-dimensional immunoglobulin models are commonly available and familiar to those skilled in the art. Computer programs are available that illustrate and display likely three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays allows analysis of the likely role of residues in the functioning of the candidate immunoglobulin sequence, i.e., analysis of residues that influence the ability of the candidate immunoglobulin to bind to the target antigen. In this way, FR residues can be selected and combined from the receptor sequences and imported so that the desired antibody characteristic, such as higher affinity for the target antigen, is achieved. In general, CDR residues are directly and substantially involved in influencing antigen binding.

[00251] A humanized antibody retains antigenic specificity similar to that of the original antibody, for example, the ability to bind to the human ILT7 antigen. However, using certain humanization methods, the binding affinity and / or specificity of the antibody for a particular antigen can be increased using “directed evolution” methods, as described by Wu et al., J. Mol. Biol., 294:151 (1999), the content of which is incorporated herein by full reference.

[00252] The anti-ILT7 antibodies or antigen-binding fragments described in this document can be tested for binding to human ILT7 by, for example, standard ELISA. Briefly, microtiter plates are coated with purified ILT7 and then blocked with bovine serum albumin. Antibody dilutions (e.g., dilutions of plasma from ILT7-immunized mice) are added to each well and incubated. The plates are washed and incubated with a secondary reagent (e.g., for human antibodies, a goat anti-human IgG Fc-specific polyclonal reagent) conjugated with horseradish peroxidase (HRP). After washing, the plates can be revealed and analyzed by a Petition 870250083106, dated 09 / 15 / 2025, pages 280 / 354 130 / 171 spectrophotometer. Sera from immunized mice can then be screened by flow cytometry for binding to a cell line expressing human ILT7, but not to a control cell line that does not express ILT7. Briefly, anti-ILT7 antibody binding can be assessed by incubating ILT7-expressing CHO cells with the anti-ILT7 antibody. The cells can be washed and binding can be detected with an anti-human IgG antibody. Flow cytometry analyses can be performed using a FACScan flow cytometry instrument (Becton Dickinson, San Jose, CA). Mice that develop the highest titers can be used for fusions.

[00253] An ELISA assay, such as the one described above, can be used to screen antibodies and therefore hybridomas that produce antibodies showing positive reactivity with the immunogen ILT7. Hybridomas that produce antibodies that bind with high affinity to ILT7 can then be subcloned and subsequently characterized. One clone from each hybridoma, which retains the reactivity of the mother cells (by ELISA), can then be selected for the formation of a cell bank and for antibody purification.

[00254] To purify anti-ILT7 antibodies, selected hybridomas can be cultured for the purification of monoclonal antibodies. The supernatants can be filtered and concentrated before affinity chromatography. The eluted IgG can be verified by gel electrophoresis and high-performance liquid chromatography to ensure purity. The buffer solution can be changed and the concentration determined. The monoclonal antibodies can be aliquoted and stored.

[00255] To determine whether selected anti-ILT7 monoclonal antibodies bind to single epitopes, each antibody can be biotinylated using commercially available reagents (Pierce, Rockford, IL). Binding of the biotinylated MAb can be detected with a streptavidin-labeled probe. Competition studies using non-ILT7 monoclonal antibodies Petition 870250083106, dated 09 / 15 / 2025, pp. 281 / 354 Labeled 131 / 171 and biotinylated monoclonal antibodies can be performed using ILT7-coated ELISA plates, as described above.

[00256] To determine the isotype of purified antibodies, isotype ELISAs can be performed using reagents specific for antibodies of a particular isotype. For example, to determine the isotype of a human monoclonal antibody, microtiter plate wells can be coated with 1 pg / mL of anti-human immunoglobulin overnight at 4 °C. After blocking with 1% BSA, the plates react with the test monoclonal antibodies or with purified isotype control antibodies at room temperature for one to two hours. The wells can then react with alkaline phosphatase-conjugated probes specific for human IgG1 or human IgM. The plates are developed and analyzed as described above.

[00257] To test the binding of monoclonal antibodies to live cells expressing ILT7, flow cytometry can be used, as described in the Examples. Briefly, cell lines expressing membrane-bound ILT7 (cultured under standard growth conditions) are mixed with various concentrations of monoclonal antibodies in PBS containing 0.1% BSA at 4°C for 1 hour. After washing, the cells react with fluorescein-labeled anti-IgG antibody under the same conditions as the primary antibody staining. Samples can be analyzed by the FACScan instrument using light and side scattering properties to identify individual cells and determine the binding of the labeled antibodies. An alternative assay using fluorescence microscopy can be used (in addition to or instead of) the flow cytometry assay. Cells can be stained exactly as described above and examined by fluorescence microscopy.This method allows visualization of individual cells, but its sensitivity may be reduced depending on the antigen density.

[00258] Anti-ILT7 antibodies or antigen-binding fragments can be further tested for reactivity with the ILT7 antigen by Petition 870250083106, dated 09 / 15 / 2025, pp. 282 / 354 132 / 171 Western blotting. Briefly, cell extracts from cells expressing ILT7 can be prepared and subjected to electrophoresis on polyacrylamide gel with sodium dodecyl sulfate. After electrophoresis, the separated antigens are transferred to nitrocellulose membranes, blocked with 20% mouse serum, and probed with the monoclonal antibodies to be tested. IgG binding can be detected using anti-IgG alkaline phosphatase and developed with BCIP / NBT substrate tablets (Sigma Chem. St. Louis County, MO).

[00259] Methods for analyzing binding affinity, cross-reactivity, and binding kinetics of various anti-ILT7 antibodies include standard assays known in the art, for example, biolayer interferometry (BLI) using, for example, the Gator system (Probe Life) or the Octet-96 system (Sartorius AG), or BIACORE™ surface plasmon resonance (SPR) analysis using a BIACORE™ 2000 SPR instrument (Biacore AB, Uppsala, Sweden). F. Pharmaceutical Compositions

[00260] Pharmaceutical compositions comprising the anti-ILT7 antibodies or antigen-binding fragments disclosed herein are also provided in this document. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments disclosed herein and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical compositions are useful in suppressing autoimmunity related to Type I IFN (e.g., IFNα) or pDCs. In some embodiments, the pharmaceutical compositions are useful in treating a disease or disorder associated with Type I IFN (e.g., IFNα) or pDCs.

[00261] In some embodiments, the pharmaceutical compositions provided in this document comprise anti-ILT7 antibodies or antigen-binding fragments provided in this document. The anti-ILT7 antibodies or Petition 870250083106, dated 09 / 15 / 2025, pages 283 / 354 133 / 171 antigen-binding fragments may be present in various concentrations. In some embodiments, the pharmaceutical compositions provided in this document comprise soluble anti-ILT7 antibodies or antigen-binding fragments provided in this document at 1-1000 mg / mL. Dosages can be easily adjusted by experts in the field; for example, a decrease in purity may necessitate an increase in dosage.

[00262] Kits for preparing pharmaceutical compositions containing the anti-ILT7 antibodies or antigen-binding fragments disclosed herein are also provided in this document. In some embodiments, the kit comprises the anti-ILT7 antibodies or antigen-binding fragments disclosed herein and a pharmaceutically acceptable carrier in one or more containers. In another embodiment, the kits may comprise the anti-ILT7 antibodies or antigen-binding fragments disclosed herein for administration to an individual. In specific embodiments, the kits comprise instructions relating to the preparation and / or administration of the anti-ILT7 antibodies or antigen-binding fragments.

[00263] In some embodiments, a pharmaceutical composition comprising anti-ILT7 antibodies or antigen-binding fragments or cells provided herein is provided in this document, wherein the composition is suitable for local administration.

[00264] Pharmaceutically acceptable vehicles that may be used in the compositions provided in this document include any and all solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic agents and absorption retardants and the like that are physiologically compatible. In some embodiments, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (e.g., by injection or infusion). Depending on the route of administration, the active ingredient (i.e., anti-ILT7 antibodies or antigen-binding fragments) may be coated with a Petition 870250083106, dated 09 / 15 / 2025, pages 284 / 354 134 / 171 material to protect the active ingredient from the action of acids and other natural conditions that may inactivate the active ingredient.

[00265] Pharmaceutical compositions or formulations that improve the stability of anti-ILT7 antibodies or antigen-binding fragments to allow for their long-term storage are also provided in this document. In some embodiments, the pharmaceutical composition or formulation disclosed in this document comprises: (a) anti-ILT7 antibodies or antigen-binding fragments disclosed in this document; (b) a buffering agent; (c) a stabilizing agent; (d) a salt; (e) a bulking agent; and / or (f) a surfactant. In some embodiments, the pharmaceutical composition or formulation is stable for at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 1 year, at least 2 years, at least 3 years, at least 5 years or more. In some embodiments, the pharmaceutical composition or formulation is stable when stored at 4°C, 25°C or 40°C.

[00266] Buffering agents useful in the pharmaceutical compositions or formulations disclosed in this document may be a weak acid or base used to maintain the acidity (pH) of a solution close to a chosen value after the addition of another acid or base. Suitable buffering agents can maximize the stability of pharmaceutical formulations by maintaining control of the formulation's pH. Suitable buffering agents can also ensure physiological compatibility or optimize solubility. Rheology, viscosity, and other properties may also depend on the formulation's pH. Common buffering agents include, but are not limited to, histidine, citrate, succinate, acetate, and phosphate. In some embodiments, a buffering agent comprises histidine (e.g., L-histidine) with isotonicity agents and potentially pH adjustment with an acid or base known in the art. In certain embodiments, the buffering agent is L-histidine.In certain embodiments, the pH of the formulation is maintained between approximately 2 and approximately 10, or between approximately 4 and approximately 8. Petition 870250083106, dated 09 / 15 / 2025, pages 285 / 354 135 / 171

[00267] Stabilizing agents are added to a pharmaceutical product to stabilize it. These agents can stabilize proteins in different ways. Common stabilizing agents include, but are not limited to, amino acids such as glycine, alanine, lysine, arginine, or threonine; carbohydrates such as glucose, sucrose, trehalose, raffinose, or maltose; polyols such as glycerol, mannitol, sorbitol; cyclodextrins or dextrans of any type and molecular weight; or PEG. In some embodiments, the stabilizing agent is chosen to maximize the stability of the polypeptide in lyophilized preparations. In certain embodiments, the stabilizing agent is sucrose and / or arginine.

[00268] Bulking agents can be added to a pharmaceutical composition or formulation to add volume and mass to the product, thereby facilitating accurate dosing and handling. Common bulking agents include, but are not limited to, lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, or magnesium stearate.

[00269] Surfactants are amphipathic substances with lyophilic and lyophobic groups. A surfactant can be anionic, cationic, zwitterionic, or nonionic. Examples of nonionic surfactants include, but are not limited to, alkyl ethoxylate, nonylphenol ethoxylate, amine ethoxylate, polyethylene oxide, polypropylene oxide, fatty alcohols such as cetyl alcohol or oleyl alcohol, cocamide MEA, cocamide DEA, polysorbates, or dodecyl dimethylamine oxide. In some embodiments, the surfactant is polysorbate 20 or polysorbate 80.

[00270] The pharmaceutical compositions disclosed in this document may also include one or more of the following: a buffer system, a preservative, a tonicity agent, a chelating agent, a stabilizer and / or a surfactant, as well as various combinations thereof. The use of preservatives, isotonic agents, chelating agents, stabilizers and surfactants in pharmaceutical compositions is well known to the expert. Reference may be made to Remington: The Science and Practice of Pharmacy, 19th edition, 1995. Petition 870250083106, dated 09 / 15 / 2025, pp. 286 / 354 136 / 171

[00271] In some embodiments, the pharmaceutical composition is an aqueous formulation. This formulation is normally a solution or a suspension, but may also include colloids, dispersions, emulsions, and multiphase materials. The term “aqueous formulation” is defined as a formulation comprising at least 50% w / w water. Similarly, the term “aqueous solution” is defined as a solution comprising at least 50% w / w water, and the term “aqueous suspension” is defined as a suspension comprising at least 50% w / w water.

[00272] In some embodiments, the pharmaceutical compositions disclosed in this document are lyophilized, to which the physician or patient adds solvents and / or diluents before use.

[00273] The pharmaceutical compositions disclosed in this document may also include a pharmaceutically acceptable antioxidant. Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol and the like; and (3) metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid and the like.

[00274] Examples of suitable aqueous and non-aqueous vehicles that can be used in the pharmaceutical compositions or formulations described in this document include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like) and suitable mixtures thereof, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Adequate flowability can be maintained, for example, by the use of coating materials such as lecithin, by maintaining the required particle size in the case of dispersions, and by the use of surfactants. Petition 870250083106, dated 09 / 15 / 2025, pp. 287 / 354 137 / 171

[00275] These compositions may also contain adjuvants, such as preservatives, humectants, emulsifying agents, and dispersing agents. The prevention of microorganisms can be ensured both by sterilization procedures, as described above, and by the inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenolsorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like in the compositions. Furthermore, prolonged absorption of the injectable pharmaceutical form can be achieved by including agents that retard absorption, such as aluminum monostearate and gelatin.

[00276] Pharmaceutically acceptable vehicles include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. The use of such media and agents for pharmaceutically active substances is known in the art. Except to the extent that any conventional media or agent is incompatible with the active compound, its use in the pharmaceutical compositions described in this document is contemplated. A pharmaceutical composition or formulation may comprise a preservative or may be preservative-free. Additional active compounds may be incorporated into the compositions.

[00277] Pharmaceutical compositions or formulations should normally be sterile and stable under manufacturing and storage conditions. The composition may be formulated as a solution, microemulsion, liposome, or other ordered structure suitable for high drug concentrations. The vehicle may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol and the like) and suitable mixtures thereof. Adequate flowability may be maintained, for example, by the use of a coating such as lecithin, by maintaining the required particle size in the case of dispersion, and by the use of surfactants. In many cases, the compositions may include Petition 870250083106, dated 09 / 15 / 2025, pp. 288 / 354 138 / 171 isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol or sodium chloride in the composition. Prolonged absorption of injectable compositions can be achieved by including an absorption-delaying agent in the composition, for example, monostearate salts and gelatin.

[00278] Sterile injectable solutions can be prepared by incorporating the active compound in the required quantity into an appropriate solvent with one or a combination of ingredients listed above, as needed, followed by microfiltration for sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the other necessary ingredients from those listed in this document. In the case of sterile powders for the preparation of sterile injectable solutions, some preparation methods are vacuum drying and lyophilization (freeze-drying), which produce a powder of the active ingredient plus any desired additional ingredient from a previously sterile filtered solution.

[00279] The amount of active ingredient that can be combined with a carrier material in the pharmaceutical compositions or formulations disclosed in this document may vary. In some embodiments, the amount of active ingredient that can be combined with a carrier material is the amount that produces a therapeutic effect. Generally, out of one hundred percent, this amount will vary from about 0.01 percent to about ninety-nine percent of the active ingredient, from about 0.1 percent to about 70 percent, or from about 1 percent to about 30 percent of the active ingredient in combination with a pharmaceutically acceptable vehicle.

[00280] The pharmaceutical compositions disclosed in this document may be prepared with carriers that protect the active ingredient against rapid release, such as a controlled-release formulation, including implants, transdermal patches, and microencapsulated delivery systems. Biodegradable and biocompatible polymers such as ethylene vinyl acetate, polyanhydrides, may be used. Petition 870250083106, dated 09 / 15 / 2025, pp. 289 / 354 139 / 171 polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Many methods for preparing such formulations are patented or generally known to those skilled in the art. See, for example, Sustained and Controlled Release Drug Delivery Systems, J.R. Robinson, ed., Marcel Dekker, Inc., New York, 1978.

[00281] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are formulated to ensure adequate distribution in vivo. For example, the blood-brain barrier (BBB) ​​excludes many highly hydrophilic compounds. To ensure that the active ingredient described in this document crosses the BBB, they can be formulated, for example, in liposomes. For methods of manufacturing liposomes, see, for example, US Patents 4,522,811; 5,374,548; and 5,399,331. Liposomes may comprise one or more fractions that are selectively transported to specific cells or organs, thus improving targeted drug delivery (see, for example, VV Ranade (1989) J. Clin. Pharmacol. 29: 685). Examples of targeting groups include folate or biotin (see, for example, US Patent 5,416,016 to Low et al.) mannosides (Umezawa et al., 1988) Biochem. Biophys. Res. Commun. 153: 1038); antibodies (PG Bloeman et al. (1995) FEBS Lett. 357: 140; M. Owais et al. (1995) Antimicrob. Agents Chemother. 39: 180); surfactant protein A receptor (Briscoe et al. (1995) Am. J. Physiol. 1233: 134); and pl20 (Schreier et al. (1994) J. Biol. Chem. 269: 9090); see also K. Keinanen; AM Laukkanen (1994) FEBS Lett. 346: 123; JJ Killion; IJ Fidler (1994) Immunomethods 4: 273. G. METHODS AND USES

[00282] The antibodies or antigen-binding fragments, compositions, and methods described in this document have numerous in vitro and in vivo applications, including, for example, reducing the release of Type I IFN by ILT7-expressing cells, such as pDCs. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are Petition 870250083106, dated 09 / 15 / 2025, pp. 290 / 354 140 / 171 humanized antibodies or antigen-binding fragments. For example, anti-ILT7 antibodies or antigen-binding fragments described in this document can be administered to cells in culture, in vitro or ex vivo, or to human individuals, for example, in vivo, to selectively inhibit the release of Type I IFN or suppress the activity of pDCs in a variety of diseases. Consequently, methods for reducing autoimmunity in an individual are provided in this document, the methods comprising administering to the individual an anti-ILT7 antibody or antigen-binding portion described in this document, so that the autoimmunity associated with Type I IFN or pDCs in the individual is reduced.

[00283] This disclosure also provides methods of using anti-ILT7 antibodies or antigen-binding fragments, polynucleotides encoding such anti-ILT7 antibodies or antigen-binding fragments, vectors comprising such polynucleotides, or pharmaceutical compositions having such antibodies or antigen-binding fragments disclosed herein in reducing cytokine release (e.g., IFN Type I) by ILT7-expressing cells, such as pDCs, or in treating a disease or disorder associated with IFN Type I or pDC-associated diseases, such as autoimmune diseases.

[00284] In some embodiments, methods are provided in this document for reducing Type I IFN (e.g., IFNα) in an individual in need thereof, the methods comprising administering to the individual a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document to reduce Type I IFN (e.g., IFNα) are provided in this document. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments provided in this document for the preparation of a medicament to reduce Type I IFN (e.g., α) are provided in this document. In some embodiments, Petition 870250083106, dated 09 / 15 / 2025, pp. 291 / 354 141 / 171 document methods for reducing Type I IFN (e.g., IFNa) in an individual who needs it, the methods comprising administering to the individual a therapeutically effective amount of the pharmaceutical compositions disclosed in this document. In some embodiments, uses of the pharmaceutical compositions disclosed in this document to reduce Type I IFN (e.g., IFNa) are provided in this document. In some embodiments, uses of the pharmaceutical compositions provided in this document for the preparation of a medicament to reduce Type I IFN (e.g., IFNa) are provided in this document.

[00285] In some embodiments, methods are provided in this document for suppressing or depleting pDCs in an individual who needs them, the methods comprising administering to the individual a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document to suppress or deplete pDCs are provided in this document. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments provided in this document for the preparation of a medicament to suppress or deplete pDCs are provided in this document. In some embodiments, methods are provided in this document for suppressing or depleting pDCs in an individual who needs them, the methods comprising administering to the individual a therapeutically effective amount of the pharmaceutical compositions disclosed in this document.In some embodiments, uses of the pharmaceutical compositions disclosed herein for suppressing or depleting pDCs are provided in this document. In some embodiments, uses of the pharmaceutical compositions provided herein for the preparation of a medicament to suppress or deplete pDCs are provided in this document. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments disclosed herein deplete pDCs in an individual who needs them. Petition 870250083106, dated 09 / 15 / 2025, pp. 292 / 354 142 / 171

[00286] In some embodiments, methods are provided in this document for reducing autoimmunity associated with Type I IFN (e.g., IFNα) or pDCs in an individual who needs them, the methods comprising administering to the individual a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document are provided in this document to reduce autoimmunity associated with Type I IFN (e.g., IFNα) or pDCs. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments provided in this document are provided in this document for the preparation of a medicament to reduce autoimmunity associated with Type I IFN (e.g., α) or pDCs.In some embodiments, methods are provided in this document for reducing autoimmunity associated with Type I IFN (e.g., α) or pDCs in an individual who needs them, the methods comprising administering to the individual a therapeutically effective amount of the pharmaceutical compositions disclosed in this document. In some embodiments, uses of the pharmaceutical compositions disclosed in this document are provided in this document to reduce autoimmunity associated with Type I IFN (e.g., α) or pDCs. In some embodiments, uses of the pharmaceutical compositions provided in this document are provided in this document for the preparation of a medicament to reduce autoimmunity associated with Type I IFN (e.g., α) or pDCs.

[00287] In some embodiments, this document provides methods for treating an autoimmune disease associated with Type I IFN (e.g., α) or pDCs in an individual who requires them, the methods comprising administering to the individual a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments disclosed in this document. In some embodiments, this document provides uses of the anti-ILT7 antibodies or fragments of Petition 870250083106, dated 09 / 15 / 2025, pages 293 / 354 143 / 171 antigen-binding antibodies disclosed in this document are used to treat an autoimmune disease associated with Type I IFN (e.g., IFNα) or pDCs. In some embodiments, uses of the anti-ILT7 antibodies or antigen-binding fragments provided in this document are provided for the preparation of a medicament to treat an autoimmune disease associated with Type I IFN (e.g., IFNα) or pDCs. In some embodiments, methods of treating an autoimmune disease associated with Type I IFN (e.g., α) or pDCs in an individual in need thereof are provided in this document, the methods comprising administering to the individual a therapeutically effective amount of the pharmaceutical compositions disclosed in this document. In some embodiments, uses of the pharmaceutical compositions disclosed in this document are provided for treating an autoimmune disease associated with Type I IFN (e.g., α) or pDCs.In some embodiments, uses of the pharmaceutical compositions provided herein are given for the preparation of a medicament to treat an autoimmune disease associated with Type I IFN (e.g., ^α) or pDCs.

[00288] As known in the art, dysregulated or excessive activation of pDCs or the release of Type I IFN (e.g., α) leads to unwanted activation of the immune system, which has been implicated in the pathogenesis of a wide variety of diseases, such as autoimmune diseases. In some embodiments, the disease or disorder associated with pDCs or α that can be treated with anti-ILT7 antibodies or antigen-binding fragments, or pharmaceutical compositions provided in this document, includes lupus; lupus erythematosus, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), and discoid lupus erythematosus (DLE); and / or lupus nephritis (LN). In some embodiments, the disease or disorder that can be treated with the anti-ILT7 antibodies or antigen-binding fragments, or pharmaceutical compositions provided in this document, is lupus. In some modalities, the disease or disorder that can be treated with anti-ILT7 antibodies or fragments of Petition 870250083106, dated 09 / 15 / 2025, pp. 294 / 354 144 / 171 antigen-binding antibodies, or pharmaceutical compositions provided in this document, are called SLE. In some embodiments, the disease or disorder that can be treated with anti-ILT7 antibodies or antigen-binding fragments, or pharmaceutical compositions provided in this document, is called CLE. In some embodiments, the disease or disorder that can be treated with anti-ILT7 antibodies or antigen-binding fragments, or pharmaceutical compositions provided in this document, is called LED. In some embodiments, the disease or disorder that can be treated with anti-ILT7 antibodies or antigen-binding fragments, or pharmaceutical compositions provided in this document, is called LN.

[00289] In some modalities, the methods provided in this document promote a beneficial therapeutic response in relation to an autoimmune response. In some modalities, the methods provided in this document result in an improvement in symptoms associated with a disease, such as a decrease in IFNα levels, a decrease in the number or activity of pDCs, or a decrease in one or more other symptoms associated with the disease. Thus, for example, an improvement in the disease may be characterized as a complete response. In some modalities, a clinical response may be assessed using screening techniques such as magnetic resonance imaging (MRI), radiography, computed tomography (CT), flow cytometry or fluorescence-activated cell sorter (FACS) analysis, histology, macroscopic pathology, and blood chemistry, including, but not limited to, techniques that measure changes detectable by ELISA, RIA, chromatography, and the like.

[00290] Actual dosage levels of the active ingredients (i.e., anti-ILT7 antibodies or antigen-binding fragments) in the pharmaceutical compositions described in this document may be varied in order to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a specific patient, composition, and route of administration, without being toxic to the patient. The selected dosage level Petition 870250083106, dated 09 / 15 / 2025, pages 295 / 354 145 / 171 will depend on a variety of pharmacokinetic factors, including the activity of the specific compositions described in this document, the route of administration, the time of administration, the rate of excretion, the duration of treatment, other medications, compounds and / or materials used in combination with the specific compositions employed, the age, sex, weight, condition, general health and previous medical history of the patient to be treated, and similar factors well known in the medical arts.

[00291] Anti-ILT7 antibodies or antigen-binding fragments can be administered as a sustained-release formulation, in which case less frequent administration is required. Dosage and frequency vary depending on the half-life of the anti-ILT7 antibodies or antigen-binding fragments in the patient. In therapeutic applications, a relatively high dosage at relatively short intervals is sometimes required until disease progression is reduced or halted, and until the patient shows partial or complete improvement of disease symptoms.

[00292] The anti-ILT7 antibodies or antigen-binding fragments or pharmaceutical compositions provided in this document may be administered to an individual by any methods known in the art, including, but not limited to, pleural administration, intravenous administration, subcutaneous administration, intranodal administration, intramuscular administration, intradermal administration, intrathecal administration, intrapleural administration, intraperitoneal administration, intracranial administration, spinal routes of administration or other parenteral routes, for example, by injection or infusion, or direct administration to the thymus.The term "parenteral administration," as used in this document, means modes of administration other than enteral and topical administration, generally by injection, and includes, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, and subcapsular injection. Petition 870250083106, dated 09 / 15 / 2025, pp. 296 / 354 146 / 171 subarachnoid, intraspinal, epidural, and intrasternal, and infusion. In some embodiments, subcutaneous administration is adopted. In some embodiments, intravenous administration is adopted. In some embodiments, oral administration is adopted. In one embodiment, the antibodies or antigen-binding fragments provided in this document are administered locally. In another embodiment, the antibodies or antigen-binding fragments provided in this document are administered systemically.

[00293] In the methods disclosed in this document, a therapeutically effective amount of the anti-ILT7 antibodies or antigen-binding fragments or pharmaceutical compositions disclosed in this document is administered to an individual who may benefit from the reduction in IFNα levels. The individual may have unwanted, dysregulated, or excessive activation of pDCs. The individual may be a mammal. In some embodiments, the individual is a human.

[00294] Anti-ILT7 antibodies or antigen-binding fragments or pharmaceutical compositions provided in this document may be administered with medical devices known in the art. For example, in some embodiments, a needle-free hypodermic injection device may be used, such as the devices disclosed in U.S. Patents Nos. 5,399,163; 5,383,851; 5,312,335; 5,064,413; 4,941,880; 4,790,824; or 4,596,556. Examples of well-known implants and modules for use described in this document include: U.S. Patent No. 4,487,603, which describes an implantable microinfusion pump for dispensing medication at a controlled rate; U.S. Patent No. 4,486,194, which describes a therapeutic device for administering medication through the skin; U.S. Patent No. 4,447,233, which describes a drug infusion pump for delivering drugs at a precise infusion rate; U.S. Patent No. 4,447.224, which describes an implantable variable-flow infusion device for continuous drug administration; U.S. Patent No. 4,439,196, which describes an osmotic drug delivery system with... Petition 870250083106, dated 09 / 15 / 2025, pp. 297 / 354 147 / 171 multi-chamber compartments; and U.S. Patent No. 4,475,196, which describes an osmotic drug delivery system. These patents are incorporated herein by reference. Many other implants, delivery systems, and modules are known to experts in the field.

[00295] In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments or pharmaceutical compositions provided in this document are administered with additional therapy. The additional therapy may be administered before, concurrently with, or after the administration of the anti-ILT7 antibodies or antigen-binding fragments, cells, or pharmaceutical compositions described in this document. Combined administration may include co-administration, either in a single pharmaceutical formulation or using separate formulations, or consecutive administration in any order, but generally within a time period such that all active agents can exert their biological activities simultaneously.A specialist in the field can easily determine appropriate regimens for administering a pharmaceutical composition described in this document and an additional combination therapy, including the timing and dosage of an additional agent to be used in a combination therapy, based on the needs of the individual being treated.

[00296] The antibodies or antigen-binding fragments provided in this document can also be used in the detection of ILT7. Also covered are methods for detecting the presence of human ILT7 antigen in a sample, or measuring the amount of human ILT7 antigen, comprising placing the sample and a control sample in contact with a monoclonal antibody, for example, a humanized monoclonal antibody, or an antigen-binding portion thereof, which binds specifically to human ILT7, under conditions that allow the formation of a complex between the antibody or antigen-binding fragment and human ILT7. The formation of a complex is then detected, where a different complex formation between the sample compared to the control sample is indicative of Petition 870250083106, dated 09 / 15 / 2025, pages 298 / 354 148 / 171 presence of human ILT7 antigen in the sample. Furthermore, the anti-ILT7 antibodies or antigen-binding fragments described in this document can be used to purify human ILT7 via immunoaffinity purification. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are used to detect cells expressing ILT7, such as pDCs. In some embodiments, the anti-ILT7 antibodies or antigen-binding fragments described in this document are used to quantify the ILT7 antigen or cells expressing ILT7. H. EXEMPLIFIED MODALITIES

[00297] Embodiment 1: An antibody or antigen-binding fragment that specifically binds to human ILT7, the antibodies or antigen-binding fragments comprising: (1) as defined by Kabat, (a) a variable light chain (VL) region comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in the VL CDRs; and / or (b) a variable heavy chain (VH) region comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in the VH CDRs; or (2) as defined by Chothia, (a) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12, and 13, respectively;or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VL CDRs; and / or (b) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VH CDRs.

[00298] Modality 2: The antibody or antigen-binding fragment of modality 1, comprising VL CDR1, VL CDR2, VL CDR3, VH Petition 870250083106, dated 09 / 15 / 2025, pp. 299 / 354 149 / 171 CDR1, VH CDR2, and VH CDR3 with amino acid sequences of SEQ ID NOS: 11, 12, 13, 14, 15, and 16, respectively, as defined by Kabat.

[00299] Modality 3: The antibody or antigen-binding fragment of modality 1, comprising VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and VH CDR3 with the amino acid sequences of SEQ ID NOs: 11, 12, 13, 17, 18 and 16, respectively, as defined by Chothia.

[00300] Embodiment 4: An antibody or antigen-binding fragment that specifically binds to human ILT7, the antigen or antigen-binding fragment comprising: (a) a VL having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 10.

[00301] Modality 5: The antibody or antigen-binding fragment of Modality 4, comprising a VL and a VH with the amino acid sequences of SEQ ID NOs: 9 and 10, respectively.

[00302] Embodiment 6: An antibody or antigen-binding fragment that specifically binds to human ILT7, the antigen or antigen-binding fragment comprising (a) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH comprising VH CDR1, VH CDR2, and VH CDR3 of a VH having the amino acid sequence of SEQ ID NO: 10.

[00303] Embodiment 7: The antibody or antigen-binding fragment according to any of Embodiments 1 to 6, wherein the antibody or antigen-binding fragment is a chimeric antibody or antigen-binding fragment, a humanized antibody or antigen-binding fragment, or a human antibody or antigen-binding fragment. Petition 870250083106, dated 09 / 15 / 2025, pages 300 / 354 150 / 171

[00304] Modality 8: The antibody or antigen-binding fragment according to Modality 7, wherein the antibody or antigen-binding fragment is a humanized antibody or antigen-binding fragment.

[00305] Modality 9: The antibody or antigen-binding fragment according to Modality 8, comprising: (a) a VL having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of any of the SEQ ID NOs: 19-22; and / or (b) a VH having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of any of the SEQ ID NOs: 23-28.

[00306] Embodiment 10: The antibody or antigen-binding fragment according to Embodiment 9, comprising: (a) a VL having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 19; and (b) a VH having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 26.

[00307] Embodiment 11: The antibody or antigen-binding fragment according to Embodiment 9, comprising: (a) a VL having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 19, the VL comprising, as defined by Kabat or Chothia, VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; and (b) a VH having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 26, the VH comprising (1) as defined by Kabat, VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively, or Petition 870250083106, dated 09 / 15 / 2025, pp. 301 / 354 151 / 171 (2) as defined by Chothia, VH CDR1, VH CDR2 and VH CDR3 having amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively.

[00308] Modality 12: The antibody or antigen-binding fragment of Modality 9, comprising a VL and a VH with amino acid sequences of (1) SEQ ID NOs: 19 and 23, respectively; (2) SEQ ID NOs: 19 and 24, respectively; (3) SEQ ID NOs: 19 and 25, respectively; (4) SEQ ID NOs: 19 and 26, respectively; (5) SEQ ID NOs: 19 and 27, respectively; (6) SEQ ID NOs: 19 and 28, respectively; (7) SEQ ID NOs: 20 and 23, respectively; (8) SEQ ID NOs: 20 and 24, respectively; (9) SEQ ID NOs: 20 and 25, respectively; (10) SEQ ID NOs: 20 and 26, respectively; (11) SEQ ID NOs: 20 and 27, respectively; (12) SEQ ID NOs: 20 and 28, respectively; (13) SEQ ID NOs: 21 and 23, respectively; (14) SEQ ID NOs: 21 and 24, respectively; (15) SEQ ID NOs: 21 and 25, respectively; (16) SEQ ID NOs: 21 and 26, respectively; (17) SEQ ID NOs: 21 and 27, respectively; (18) SEQ ID NOs: 21 and 28, respectively; (19) SEQ ID NOs: 22 and 23, respectively;(20) SEQ ID NOs: 22 and 24, respectively; (21) SEQ ID NOs: 22 and 25, respectively; (22) SEQ ID NOs: 22 and 26, respectively; (23) SEQ ID NOs: 22 and 27, respectively; or (24) SEQ ID NOs: 22 and 28, respectively.;

[00309] Embodiment 13: The antibody or antigen-binding fragment according to Embodiment 12, comprising a VL with the amino acid sequence SEQ ID NO: 19 and a VH with the amino acid sequence SEQ ID NOs: 26.

[00310] Embodiment 14: The antibody or antigen-binding fragment according to any of Embodiments 1 to 13, wherein the antibody or antigen-binding fragment is a Fab, a Fab', an F(ab')2, an Fv, an scFv, a (scFv)2, a single-domain antibody (sdAb) or a heavy-chain antibody (HCAb).

[00311] Modality 15: The antibody or antigen-binding fragment according to any of Modalities 1 to 13, wherein the Petition 870250083106, dated 09 / 15 / 2025, pp. 302 / 354 152 / 171 antibody or antigen-binding fragment is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody.

[00312] Mode 16: The antibody or antigen-binding fragment according to Mode 15, where the antibody is an IgG1 antibody.

[00313] Modality 17: The antibody or antigen-binding fragment according to Modality 16, comprising a constant region of the light chain (CL) with at least 85% sequence identity with kappa CL (Ck; SEQ ID NO: 29).

[00314] Modality 18: The antibody or antigen-binding fragment according to Modality 16, comprising a constant region of the light chain (LC) with at least 85% sequence identity to CL lambda (CA; SEQ ID NO: 30).

[00315] Modality 19: The antibody or antigen-binding fragment according to Modality 16, comprising a constant region of the heavy chain (CH) having at least 85% sequence identity with the amino acid sequence of any of the SEQ ID NOs: 31 and 40-44.

[00316] Embodiment 20: The antibody or antigen-binding fragment according to any of Embodiments 16 to 19, wherein the constant region of the IgG1 antibody heavy chain (HC) comprises a wild-type IgG1 HC, or comprises at least one amino acid mutation that enhances the antibody's ADCC (antibody-dependent cellular cytotoxicity) or ADCP (antibody-dependent cellular phagocytosis).

[00317] Modality 21: The antibody or antigen-binding fragment according to Modality 20, wherein the CH region of the IgG1 antibody has an amino acid substitution at L234, L235, G236, S239, F243, H268, D270, R292, S298, Y300, V305, K326, A330, I332, E333, K334, P396 or any combination thereof, numbered according to the EU Index. Petition 870250083106, dated 09 / 15 / 2025, pages 303 / 354 153 / 171

[00318] Modality 22: The antibody or antigen-binding fragment according to Modality 20, wherein the CH region of the IgG1 antibody has an amino acid substitution that is L234Y, L235Q, L235V, G236A, G236W, S239D, S239M, F243L, H268D, D270E, R292P, S298A, Y300L, V305I, K326D, A330M, A330L, I332E, E333A, K334A, K334E or P396L, or any combination thereof, numbered according to the EU Index.

[00319] Modality 23: The antibody or antigen-binding fragment according to Modality 20, wherein the CH region of the IgG1 antibody is modified by amino acid substitutions that are (i) S298A, E333A and K334A; (ii) S239D and I332E; (iii) S239D, A330L and I332E; (iv) G236A; (v) G236A, S239D and I332E; (vi) G236A, A330L and I332E; (vii) G236A, S239D, A330L and I332E; (viii) F243L, R292P, Y300L, V305I and P396L; ...

Claims

CLAIMS 1. Antibody or antigen-binding fragment specifically binding to human ILT7, the antibodies or antigen-binding fragments characterized in that they comprise: (1) as defined by Kabat, (a) a variable light chain (VL) region comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in the VL CDRs; and / or (b) a variable heavy chain (VH) region comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in the VH CDRs; and / or (2) as defined by Chothia, (a) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13,respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VL CDRs; and / or (b) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively; or a variant thereof having up to about 5 amino acid substitutions, additions and / or deletions in VH CDRs.

2. Antibody or antigen-binding fragment, according to claim 1, characterized in that it comprises VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and VH CDR3, having the amino acid sequences of SEQ ID NOs: 11, 12, 13, 14, 15 and 16, respectively, as defined by Kabat.

3. Antibody or antigen-binding fragment, according to claim 1, characterized in that it comprises VL CDR1, VL CDR2, VL CDR3, VH CDR1, VH CDR2 and VH CDR3, having the sequences of Petition 870250083106, dated 09 / 15 / 2025, page 323 / 354 2 / 12 amino acids of SEQ ID NOS: 11, 12, 13, 17, 18 and 16,respectively, as defined by Chothia.

4. Antibody or antigen-binding fragment that specifically binds to human ILT7, the antibodies or antigen-binding fragments characterized in that they comprise: (a) a VL having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH having at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO:

10.

5. Antibody or antigen-binding fragment according to claim 4, characterized in that they comprise a VL and a VH having the amino acid sequences of SEQ ID NOs: 9 and 10, respectively.

6. Antibody or antigen-binding fragment that binds specifically to human ILT7, the antibody or antigen-binding fragment characterized in that it comprises (a) a VL comprising VL CDR1,VL CDR2 and VL CDR3 of a VL having the amino acid sequence of SEQ ID NO: 9; and / or (b) a VH comprising VH CDR1, VH CDR2 and VH CDR3 of a VH having the amino acid sequence of SEQ ID NO:

10.

7. Antibody or antigen-binding fragment, according to any one of claims 1 to 6, characterized in that the antibody or antigen-binding fragment is a chimeric antibody or antigen-binding fragment, a humanized antibody or antigen-binding fragment, or a human antibody or antigen-binding fragment.

8. Antibody or antigen-binding fragment, according to claim 7, characterized in that the antibody or fragment Petition 870250083106, dated 09 / 15 / 2025, p. 324 / 354 3 / 12 antigen-binding antibody is a humanized antibody or antigen-binding fragment.

9. Antibody or antigen-binding fragment according to claim 8, characterized in that it comprises: (a) a VL with at least 85%,at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of any of the SEQ ID NOs: 19-22; and / or (b) a VH with at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid of any of the SEQ ID NOs: 23-28.

10. Antibody or antigen-binding fragment according to claim 9, characterized in that it comprises: (a) a VL with at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 19; and (b) a VH with at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO:

26.

11. Antibody or antigen-binding fragment according to claim 9, characterized in that it comprises: (a) a VL with at least 85%, at least 90%, at least 95%,at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 19, VL comprising, as defined by Kabat or Chothia, VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively; and (b) a VH with at least 85%, at least 90%, at least 95%, at least 98% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 26, the VH comprising (1) as defined by Kabat, VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of SEQ ID NOs: 14, 15 and 16, respectively, or (2) as defined by Petition 870250083106, dated 09 / 15 / 2025, p. 325 / 354 4 / 12 Chothia, VH CDR1, VH CDR2 and VH CDR3 having amino acid sequences of SEQ ID NOs: 17, 18 and 16, respectively.

12. Antibody or antigen-binding fragment according to claim 9, characterized in that it comprises a VL and a VH having the amino acid sequences of (1) SEQ ID NOs: 19 and 23,respectively; (2) SEQ ID NOs: 19 and 24, respectively; (3) SEQ ID NOs: 19 and 25, respectively; (4) SEQ ID NOs: 19 and 26, respectively; (5) SEQ ID NOs: 19 and 27, respectively; (6) SEQ ID NOs: 19 and 28, respectively; (7) SEQ ID NOs: 20 and 23, respectively; (8) SEQ ID NOs: 20 and 24, respectively; (9) SEQ ID NOs: 20 and 25, respectively; (10) SEQ ID NOs: 20 and 26, respectively; (11) SEQ ID NOs: 20 and 27, respectively; (12) SEQ ID NOs: 20 and 28, respectively; (13) SEQ ID NOs: 21 and 23, respectively; (14) SEQ ID NOs: 21 and 24, respectively; (15) SEQ ID NOs: 21 and 25, respectively; (16) SEQ ID NOs: 21 and 26, respectively; (17) SEQ ID NOs: 21 and 27, respectively; (18) SEQ ID NOs: 21 and 28, respectively; (19) SEQ ID NOs: 22 and 23, respectively; (20) SEQ ID NOs: 22 and 24, respectively; (21) SEQ ID NOs: 22 and 25, respectively; (22) SEQ ID NOs: 22 and 26, respectively; (23) SEQ ID NOs: 22 and 27, respectively; or (24) SEQ ID NOs: 22 and 28,respectively.

13. Antibody or antigen-binding fragment, according to claim 12, characterized in that it comprises a VL and a VH having the amino acid sequences of SEQ ID NOs: 19 and 26, respectively.

14. Antibody or antigen-binding fragment, according to any one of claims 1 to 13, characterized in that the antibody or antigen-binding fragment is a Fab, a Fab', an F(ab')2, an Fv, an scFv, a (scFv)2, a single-domain antibody (sdAb) or a heavy-chain antibody (HCAb).

15. Antibody or antigen-binding fragment, according to any one of claims 1 to 13, characterized in that Petition 870250083106, dated 09 / 15 / 2025, p. 326 / 354 5 / 12 antibody or antigen-binding fragment is an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody.

16. Antibody or antigen-binding fragment according to claim 15,characterized in that the antibody is an IgG1 antibody.

17. Antibody or antigen-binding fragment according to claim 16, characterized in that it comprises a constant region of the light chain (CL) with at least 85% sequence identity with kappa CL (Ck; SEQ ID NO: 29).

18. Antibody or antigen-binding fragment according to claim 16, characterized in that it comprises a constant region of the light chain (CL) with at least 85% sequence identity with lambda CL (Ck; SEQ ID NO: 30).

19. Antibody or antigen-binding fragment according to claim 16, characterized in that it comprises a constant region of the heavy chain (CH) with at least 85% sequence identity with the amino acid sequence of any of the SEQ ID NOs: 31 and 40-44.

20. Antibody or antigen-binding fragment according to any one of claims 16 to 19,characterized in that the constant region of the heavy chain (CH) of the IgG1 antibody comprises a wild-type IgG1 CH, or comprises at least one amino acid mutation that enhances the ADCC (antibody-dependent cellular cytotoxicity) or ADCP (antibody-dependent cellular phagocytosis) of the antibody.

21. Antibody or antigen-binding fragment according to claim 20, characterized in that the CH region of the IgG1 antibody has an amino acid substitution at L234, L235, G236, S239, F243, H268, D270, R292, S298, Y300, V305, K326, A330, I332, E333, K334, P396 or any combination thereof, numbered according to the EU Index. Petition 870250083106, dated 15 / 09 / 2025, p. 327 / 354 6 / 12 22. Antibody or antigen-binding fragment according to claim 20, characterized in that the CH region of the IgG1 antibody has an amino acid substitution that is L234Y, L235Q, L235V, G236A, G236W, S239D, S239M, F243L, H268D, D270E, R292P,S298A, Y300L, V305I, K326D, A330M, A330L, I332E, E333A, K334A, K334E or P396L, or any combination thereof, numbered according to the EU Index.

23. Antibody or antigen-binding fragment according to claim 20, characterized in that the CH region of the IgG1 antibody is modified by amino acid substitutions that are (i) S298A, E333A and K334A; (ii) S239D and I332E; (iii) S239D, A330L and I332E; (iv) G236A; (v) G236A, S239D and I332E; (vi) G236A, A330L and I332E; (vii) G236A, S239D, A330L and I332E; (viii) F243L, R292P, Y300L, V305I and P396L; (ix) L235V, F243L, R292P, Y300L and P396L; (x) L234Y, L235Q, G236W, S239M, H268D, D270E and S298A; or (xi) D270E, K326D, A330M and K334E, numbered according to the EU Index.

24. Antibody or antigen-binding fragment according to claim 23, characterized in that the CH region has the amino acid sequence of any of the SEQ ID NOs: 45-64.

25. Antibody or antigen-binding fragment,According to claim 1, characterized in that it comprises: a VL with the amino acid sequence SEQ ID NO: 19; a VH with the amino acid sequence SEQ ID NO: 26; and a CH with the amino acid sequence SEQ ID NO:

55.

26. Antibody or antigen-binding fragment, according to claim 1, characterized in that it comprises: a VL with the amino acid sequence SEQ ID NO: 19; a VH with the amino acid sequence SEQ ID NO: 26; a CL with the amino acid sequence SEQ ID NO: 30; and a CH with the amino acid sequence SEQ ID NO:

55. Petition 870250083106, dated 09 / 15 / 2025, p. 328 / 354 7 / 12 27. Antibody or antigen-binding fragment, according to any one of claims 16 to 26,characterized in that the Fc region of the IgG1 antibody is afucosylated.

28. Antibody or antigen-binding fragment thereof that competes with the antibody or antigen-binding fragment according to any one of claims 1 to 27, characterized in that it is for binding to human ILT7.

29. Antibody or antigen-binding fragment according to any one of claims 1 to 28, characterized in that the antibody or antigen-binding fragment is a bispecific antibody or a multispecific antibody.

30. Antibody or antigen-binding fragment according to any one of claims 1 to 29, characterized in that the antibody or antigen-binding fragment is a monoclonal antibody or antigen-binding fragment.

31. Antibody or antigen-binding fragment according to any one of claims 1 to 30,characterized in that the antibody or antigen-binding fragment: (1) binds to human ILT7 with a Kd of 500 nM or less, measured by SPR; (2) does not specifically link to LILR family member LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3 or LILB5; (3) inhibits the release of interferon alpha (α) by peripheral blood mononuclear cells (PBMCs); (4) selectively binds to plasmacytoid dendritic cells (pDCs) in human PBMCs; (5) exhibits ADCC activity dependent on natural killer (NK) cells against cells expressing ILT7; Petition 870250083106, dated 09 / 15 / 2025, pp. 329 / 354 8 / 12 (6) exhibits ADCC activity dependent on neutrophils against cells expressing ILT7; or (7) exhibits ADCP activity dependent on macrophages against cells expressing ILT7; or any combination of (1)-(7).

32. Antibody or antigen-binding fragment that specifically binds to the protease domain of human ILT7, characterized in that the antibody or antigen-binding fragment: (1) binds to human ILT7 with a Kd of 500 nM or less, measured by SPR; (2) does not specifically bind to LILR family members LILRA1, LILRA2 / ILT1, LILRA3 / ILT6, LILRA5 / ILT11, LILRA6 / ILT8, LILRB1 / ILT2, LILRB2 / ILT4, LILRB3 / ILT5, LILRB4 / ILT3 or LILB5; (3) inhibits α release by PBMCs; (4) selectively binds to pDCs in human PBMCs; (5) exhibits NK-dependent ADCC activity against cells expressing ILT7; (6) exhibits neutrophil-dependent ADCC activity against ILT7-expressing cells; or (7) exhibits macrophage-dependent ADCP activity against ILT7-expressing cells; or any combination of (1)-(7).

33. Antibody or antigen-binding fragment according to claim 31 or 32, characterized in that the antibody or antigen-binding fragment: (1) inhibits the release of ^α by CpG-stimulated PBMCs in vitro with an EC50 of 1 nM or less; (2) exhibits NK-dependent ADCC activity against ILT7-expressing cells with an EC50 of 0.01 nM or less; (3) exhibits neutrophil-dependent ADCC activity against ILT7-expressing cells with an EC50 of 100 nM or less; Petition 870250083106, dated 09 / 15 / 2025, p.330 / 354 9 / 12 (4) exhibits macrophage-dependent ADCP activity against ILT7-expressing cells with an EC50 of 10 nM or less; or (5) exhibits macrophage-dependent ADCP activity against ILT7-expressing cells with a maximum phagocytic index of 20% or higher; or any combination of (1)-(5). 34.Antibody or antigen-binding fragment, according to claim 33, characterized in that the antibody or antigen-binding fragment: (1) inhibits the release of ^α by PBMCs with an EC50 ranging from 0.01 nM to 0.1 nM; (2) exhibits NK-dependent ADCC activity against ILT7-expressing cells with an EC50 ranging from 0.001 nM to 0.01 nM; (3) exhibits neutrophil-dependent ADCC activity against ILT7-expressing cells with an EC50 ranging from 1 nM to 50 nM; (4) exhibits macrophage-dependent ADCP activity against ILT7-expressing cells with an EC50 ranging from 0.5 nM to 5 nM; or (5) exhibits macrophage-dependent ADCP activity against ILT7-expressing cells with a maximum phagocytic index ranging from 20% to 80%; or any combination of (1)-(5). 35.Antibody or antigen-binding fragment, according to any one of claims 31 to 34, characterized in that the antibody or antigen-binding fragment exhibits neutrophil-dependent ADCC activity.

36. Polynucleotide characterized in that it encodes a polypeptide of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35.

37. Vector characterized in that it comprises the polynucleotide defined according to claim 36. Petition 870250083106, dated 09 / 15 / 2025, pp. 331 / 354 10 / 12 38. Host cell characterized in that it comprises the polynucleotide defined according to claim 36, or the vector defined according to claim 37. 39.Host cell according to claim 38, characterized in that the host cell: (1) overexpresses N-acetylglucosaminyltransferase III (GnTIII), (2) lacks α-1,6-fucosyltransferase (FUT8), or (3) has low fucose content, or any combination of (1)-(3).

40. Method for producing an antibody or antigen-binding fragment that specifically binds to human ILT7, the method characterized in that it comprises culturing the host cell defined according to claim 38 or 39 in a culture under conditions that permit expression of the antibody or antibody fragment.

41. Method according to claim 40, characterized in that it further comprises isolating the antibody from the culture. 42.Pharmaceutical composition characterized in that it comprises a therapeutically effective amount of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, and a pharmaceutically acceptable vehicle.

43. Method for reducing type I interferon (IFN) in an individual in need of it, the method characterized in that it comprises administering to the individual a therapeutically effective amount of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35.

44. Method, according to claim 43, characterized in that the type I interferon is α.

45. Method for suppressing or depleting pDCs in an individual in need of it, the method characterized in that it comprises administering to the individual a therapeutically effective amount of the antibody. Petition 870250083106, dated 09 / 15 / 2025, p.332 / 354 11 / 12 or defined antigen-binding fragment according to any one of claims 1 to 35.

46. Method for reducing autoimmunity in an individual in need thereof, the method characterized in that it comprises administering to the individual an effective amount of the antibody or defined antigen-binding fragment according to any one of claims 1 to 35.

47. Method, according to any one of claims 43 to 46, characterized in that the individual has an autoimmune disease.

48. Method for treating an autoimmune disease associated with Type I IFN or pDCs in an individual in need thereof, the method characterized in that it comprises administering to the individual a therapeutically effective amount of the antibody or defined antigen-binding fragment according to any one of claims 1 to 35. 49.

50. Method according to claim 47 or 48, characterized in that the autoimmune disease is systemic lupus erythematosus (SLE).

51. Method according to any one of claims 43 to 49, characterized in that it further comprises administering additional therapy to the individual.

52. Method according to any one of claims 43 to 50, characterized in that the individual is a human.

53. Use of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, characterized in that it is for the reduction of type I IFN.

54. Use according to claim 52 or 53, characterized in that the type I IFN is ^α. Petition 870250083106, dated 09 / 15 / 2025, pp. 333 / 354 12 / 12 55.Use of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, characterized in that it is for the suppression or depletion of pDCs.

56. Use of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, characterized in that it is for the preparation of a medicament to suppress or deplete pDCs.

57. Use of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, characterized in that it is for the reduction of autoimmunity.

58. Use of the antibody or antigen-binding fragment, defined according to any one of claims 1 to 35, characterized in that it is for the preparation of a medicament for the reduction of autoimmunity. 59.Use of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, characterized in that it is used in the treatment of an autoimmune disease associated with type I IFN or pDCs.

60. Use of the antibody or antigen-binding fragment defined according to any one of claims 1 to 35, characterized in that it is a preparation of a medicament for treating an autoimmune disease associated with type I IFN or pDCs.

61. Use according to claim 59 or 60, characterized in that the autoimmune disease is SLE.

Images